Study protocol: Whole genome sequencing Implementation in standard Diagnostics for Every cancer patient (WIDE)

Abstract

Background ‘Precision oncology’ can ensure the best suitable treatment at the right time by tailoring treatment towards individual patient and comprehensive tumour characteristics. In current molecular pathology, diagnostic tests which are part of the standard of care (SOC) only cover a limited part of the spectrum of genomic changes, and often are performed in an iterative way. This occurs at the expense of valuable patient time, available tissue sample, and interferes with ‘first time right’ treatment decisions. Whole Genome Sequencing (WGS) captures a near complete view of genomic characteristics of a tumour in a single test. Moreover, WGS facilitates faster implementation of new treatment relevant biomarkers. At present, WGS mainly has been applied in study settings, but its performance in a routine diagnostic setting remains to be evaluated. The WIDE study aims to investigate the feasibility and validity of WGS-based diagnostics in clinical practice. Methods 1200 consecutive patients in a single comprehensive cancer centre with (suspicion of) a metastasized solid tumour will be enrolled with the intention to analyse tumour tissue with WGS, in parallel to SOC diagnostics. Primary endpoints are (1) feasibility of implementation of WGS-based diagnostics into routine clinical care and (2) clinical validation of WGS by comparing identification of treatment-relevant variants between WGS and SOC molecular diagnostics. Secondary endpoints entail (1) added clinical value in terms of additional treatment options and (2) cost-effectiveness of WGS compared to SOC diagnostics through a Health Technology Assessment (HTA) analysis. Furthermore, the (3) perceived impact of WGS-based diagnostics on clinical decision making will be evaluated through questionnaires. The number of patients included in (experimental) therapies initiated based on SOC or WGS diagnostics will be reported with at least 3 months follow-up. The clinical efficacy is beyond the scope of WIDE. Key performance indicators will be evaluated after every 200 patients enrolled, and procedures optimized accordingly, to continuously improve the diagnostic performance of WGS in a routine clinical setting. Discussion WIDE will yield the optimal conditions under which WGS can be implemented in a routine molecular diagnostics setting and establish the position of WGS compared to SOC diagnostics in routine clinical care.

Bringing Onco-Innovation to Europe’s Healthcare Systems: The Potential of Biomarker Testing, Real World Evidence, Tumour Agnostic Therapies to Empower Personalised Medicine

“…There are opportunities still to be explored—such as providing simpler testing kits for complex conditions, and notably the development of blood biopsy, or the convergence of complex test offerings with predictive protein-, genetic- and epigenetic-based biomarkers or NGS panels, or the development of predictive potential of prognostic tests (effectively as companion diagnostics) with emerging drugs [ 11 , 24 , 25 ].…”

“…Frequently mentioned barriers to assessing TAx included the lack of comparative effectiveness, poorly characterized prognostic value of the genomic alteration defining the tumour-agnostic approach, and limited knowledge on natural history of identified patients’ populations [ 25 , 26 , 29 ]. Lack of clarity in the diagnosis pathway, the use of surrogate endpoints (without evidence on the drug’s efficacy on progression-free survival and overall survival), inappropriate design, low prevalence or low number of patients enrolled in studies, often with heterogeneity of previous treatment, were also highlighted.…”

“…Lack of clarity in the diagnosis pathway, the use of surrogate endpoints (without evidence on the drug’s efficacy on progression-free survival and overall survival), inappropriate design, low prevalence or low number of patients enrolled in studies, often with heterogeneity of previous treatment, were also highlighted. The innate complexity of the healthcare sector and lack of appropriate regulation were seen as further obstacles [ 25 ].…”

“…Fragmentation and low prevalence of appropriately digitalised systems currently inhibit collection of data, with many hospitals and centres still focused on financial accounting and working on paper. Policy decisions are needed to initiate improvements, and funding is a further challenge [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ].…”

“…Opportunities for patients are lost when science is progressing faster than the “system”, impeding the development and best use of novel treatment options. Instead of considering that analysing personal health data is a risk to individuals, it should be accepted that the reverse is the case: Not analysing personal health data is a risk to individuals [ 23 , 25 ].…”