Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time

Dhondt, Bert; Bleser, Elise De; Claeys, Tom; Buelens, Sarah; Lumen, Nicolaas; Vandesompele, Jo; Beckers, Anneleen; Fonteyne, Valérie; Eecken, Kim Van der; Bruycker, Aurélie De; Paul, Jérôme; Gramme, Pierre; Ost, Piet

doi:10.1007/s00345-018-2609-8

Cited by 25 publications

(15 citation statements)

References 28 publications

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“…In contrast to these findings, a 2019 study by Dhondt et al [31] reported that a multivariate model trained with clinical parameters and serum-derived small RNA sequencing data had no predictive ability to distinguish between OMPC and PMPC cancer patients. The range of expression values between the discovery and validation cohort changed for some of the miRNA targets, and none of the 41 miRNA targets was differentially expressed between oligometastatic and polymetastatic PC patients in the validation cohort.…”

Section: Micro Ribo-nucleic Acid (Mirna)mentioning

confidence: 91%

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Exploring miRNA Signature and Other Potential Biomarkers for Oligometastatic Prostate Cancer Characterization: The Biological Challenge behind Clinical Practice. A Narrative Review

Corrao

Zaffaroni

Bergamaschi

et al. 2021

Cancers

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In recent years, a growing interest has been directed towards oligometastatic prostate cancer (OMPC), as patients with three to five metastatic lesions have shown a significantly better survival as compared with those harboring a higher number of lesions. The efficacy of local ablative treatments directed on metastatic lesions (metastases-directed treatments) was extensively investigated, with the aim of preventing further disease progression and delaying the start of systemic androgen deprivation therapies. Definitive diagnosis of prostate cancer is traditionally based on histopathological analysis. Nevertheless, a bioptic sample—static in nature—inevitably fails to reflect the dynamics of the tumor and its biological response due to the dynamic selective pressure of cancer therapies, which can profoundly influence spatio-temporal heterogeneity. Furthermore, even with new imaging technologies allowing an increasingly early detection, the diagnosis of oligometastasis is currently based exclusively on radiological investigations. Given these premises, the development of minimally-invasive liquid biopsies was recently promoted and implemented as predictive biomarkers both for clinical decision-making at pre-treatment (baseline assessment) and for monitoring treatment response during the clinical course of the disease. Through liquid biopsy, different biomarkers, commonly extracted from blood, urine or saliva, can be characterized and implemented in clinical routine to select targeted therapies and assess treatment response. Moreover, this approach has the potential to act as a tissue substitute and to accelerate the identification of novel and consistent predictive analytes cost-efficiently. However, the utility of tumor profiling is currently limited in OMPC due to the lack of clinically validated predictive biomarkers. In this scenario, different ongoing trials, such as the RADIOSA trial, might provide additional insights into the biology of the oligometastatic state and on the identification of novel biomarkers for the outlining of true oligometastatic patients, paving the way towards a wider ideal approach of personalized medicine. The aim of the present narrative review is to report the current state of the art on the solidity of liquid biopsy-related analytes such as CTCs, cfDNA, miRNA and epi-miRNA, and to provide a benchmark for their further clinical implementation. Arguably, this kind of molecular profiling could refine current developments in the era of precision oncology and lead to more refined therapeutic strategies in this subset of oligometastatic patients.

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Section: Micro Ribo-nucleic Acid (Mirna)mentioning

confidence: 91%

“…However, probably due to the underestimation of the real metastatic burden with the standard imaging methods, almost 30% of patients treated with MDT experiment a rapid progression to polymetastatic prostate cancer (PMPC) within 1 year [31].…”

Section: Burden Of Diseasementioning

confidence: 99%

Exploring miRNA Signature and Other Potential Biomarkers for Oligometastatic Prostate Cancer Characterization: The Biological Challenge behind Clinical Practice. A Narrative Review

Corrao

Zaffaroni

Bergamaschi

et al. 2021

Cancers

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“…The search for biomarkers indicative of OMD is an active research area, with preclinical and translational studies assessing blood-based biomarkers such as microRNA expression and circulating free DNA; tissue-based biomarkers such as mutational status and intratumoural heterogeneity; and radiomic parameters [79][80][81][82]. Ideally, integration of these categories of biomarkers into a multi-systems predictions model will lead to a more precise algorithm for defining OMD than the cur-rently most often used number of metastatic lesions, and thus aid in assigning the appropriate treatment.…”

Section: Statementmentioning

confidence: 99%

Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document

Lievens

Gückenberger

Gomez

et al. 2020

Radiotherapy and Oncology

427

278

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Background: Recognizing the rapidly increasing interest and evidence in using metastasis-directed radiotherapy (MDRT) for oligometastatic disease (OMD), ESTRO and ASTRO convened a committee to establish consensus regarding definitions of OMD and define gaps in current evidence. Methods: A systematic literature review focused on curative intent MDRT was performed in Medline, Embase and Cochrane. Subsequent consensus opinion, using a Delphi process, highlighted the current state of evidence and the limitations in the available literature. Results: Available evidence regarding the use of MDRT for OMD mostly derives from retrospective, singlecentre series, with significant heterogeneity in patient inclusion criteria, definition of OMD, and outcomes reported. Consensus was reached that OMD is largely independent of primary tumour, metastatic location and the presence or length of a disease-free interval, supporting both synchronous and metachronous OMD. In the absence of clinical data supporting a maximum number of metastases and organs to define OMD, and of validated molecular biomarkers, consensus supported the ability to deliver safe and clinically meaningful radiotherapy with curative intent to all metastatic sites as a minimum requirement for defining OMD in the context of radiotherapy. Systemic therapy induced OMD was identified as a distinct state of OMD. High-resolution imaging to assess and confirm OMD is crucial, including brain imaging when indicated. Minimum common endpoints such as progression-free and overall survival, local control, toxicity and quality-of-life should be reported; uncommon endpoints as deferral of systemic therapy and cost were endorsed. Conclusion: While significant heterogeneity exists in the current OMD definitions in the literature, consensus was reached on multiple key questions. Based on available data, OMD can to date be defined as 1-5 metastatic lesions, a controlled primary tumor being optional, but where all metastatic sites must be safely treatable. Consistent definitions and reporting are warranted and encouraged in ongoing trials and reports generating further evidence to optimize patient benefits.

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“…Despite these advances, many challenges remain and require well-designed clinical trials and translational research activities: Limited progress has been made in understanding and defining OMD based on biology, i.e. in recognizing patients with truly limited metastatic capacity, based on OMD-specific biomarkers [138][139][140][141][142]: external or independent validation has been either unsuccessful or is still lacking.…”

Section: Radiation Oncology and Multimodal Treatments Oligometastasismentioning

confidence: 99%

X-change symposium: status and future of modern radiation oncology—from technology to biology

et al. 2021

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Future radiation oncology encompasses a broad spectrum of topics ranging from modern clinical trial design to treatment and imaging technology and biology. In more detail, the application of hybrid MRI devices in modern image-guided radiotherapy; the emerging field of radiomics; the role of molecular imaging using positron emission tomography and its integration into clinical routine; radiation biology with its future perspectives, the role of molecular signatures in prognostic modelling; as well as special treatment modalities such as brachytherapy or proton beam therapy are areas of rapid development. More clinically, radiation oncology will certainly find an important role in the management of oligometastasis. The treatment spectrum will also be widened by the rational integration of modern systemic targeted or immune therapies into multimodal treatment strategies. All these developments will require a concise rethinking of clinical trial design. This article reviews the current status and the potential developments in the field of radiation oncology as discussed by a panel of European and international experts sharing their vision during the “X-Change” symposium, held in July 2019 in Munich (Germany).

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Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time

Cited by 25 publications

References 28 publications

Exploring miRNA Signature and Other Potential Biomarkers for Oligometastatic Prostate Cancer Characterization: The Biological Challenge behind Clinical Practice. A Narrative Review

Exploring miRNA Signature and Other Potential Biomarkers for Oligometastatic Prostate Cancer Characterization: The Biological Challenge behind Clinical Practice. A Narrative Review

Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document

X-change symposium: status and future of modern radiation oncology—from technology to biology

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