Dataset Information

Personalized Treatment Selection and Disease Monitoring Using Circulating Tumor DNA Profiling in Real-World Cancer Patient Management.

ABSTRACT: Circulating tumor DNA (ctDNA) in the blood plasma of cancer patients is an emerging biomarker used across oncology, facilitating noninvasive disease monitoring and genetic profiling at various disease milestones. Digital droplet PCR (ddPCR) technologies have demonstrated high sensitivity and specificity for robust ctDNA detection at relatively low costs. Yet, their value for ctDNA-based management of a broad population of cancer patients beyond clinical trials remains elusive. We developed mutation-specific ddPCR assays that were optimized for their use in real-world cancer management, covering 12 genetic aberrations in common cancer genes, such as EGFR, BRAF, KIT, KRAS, and NRAS. We assessed the limit of detection (LOD) and the limit of blank (LOB) for each assay and validated their performance for ctDNA detection using matched tumor sequencing. We applied our custom ddPCR assays to 352 plasma samples from 96 patients with solid tumors. Mutation detection in plasma was highly concordant with tumor sequencing, demonstrating high sensitivity and specificity across all assays. In 20 cases, radiographic cancer progression was mirrored by an increase of ctDNA concentrations or the occurrence of novel mutations in plasma. Moreover, ctDNA profiling at diagnosis and during disease progression reflected personalized treatment selection through the identification of actionable gene targets in 20 cases. Collectively, our work highlights the potential of ctDNA assessment by sensitive ddPCR for accurate disease monitoring, robust identification of resistance mutations, and upfront treatment selection in patients with solid tumors. We envision an increasing future role for ctDNA profiling within personalized cancer management in daily clinical routine.

SUBMITTER: Wehrle J

PROVIDER: S-EPMC7459590 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Personalized Treatment Selection and Disease Monitoring Using Circulating Tumor DNA Profiling in Real-World Cancer Patient Management.

Wehrle Julius J Philipp Ulrike U Jolic Martina M Follo Marie M Hussung Saskia S Waldeck Silvia S Deuter Max M Rassner Michael M Braune Jan J Rawluk Justyna J Greil Christine C Waller Cornelius F CF Becker Heiko H Duque-Afonso Jesús J Illert Anna-L AL Fritsch Ralph M RM Meiss Frank F Duyster Justus J von Bubnoff Nikolas N Scherer Florian F

Diagnostics (Basel, Switzerland) 20200802 8

<h4>Background</h4>Circulating tumor DNA (ctDNA) in the blood plasma of cancer patients is an emerging biomarker used across oncology, facilitating noninvasive disease monitoring and genetic profiling at various disease milestones. Digital droplet PCR (ddPCR) technologies have demonstrated high sensitivity and specificity for robust ctDNA detection at relatively low costs. Yet, their value for ctDNA-based management of a broad population of cancer patients beyond clinical trials remains elusive. ...[more]

PMID: 32748806

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Project description:Melanoma currently lacks a reliable blood-based biomarker of disease activity, although circulating tumor DNA (ctDNA) may fill this role. We investigated the clinical utility (i.e., impact on clinical outcomes and interpretation of radiographic data) of measuring ctDNA in patients with metastatic or high-risk resected melanoma. Patients were prospectively accrued into ≥ 1 of three cohorts, as follows. Cohort A: patients with radiographically measurable metastatic melanoma who underwent comparison of ctDNA measured by a BEAMing digital PCR assay to tissue mutational status and total tumor burden; when appropriate, determinations about initiation of targeted therapy were based on ctDNA data. Cohorts B and C: patients with BRAF- or NRAS-mutant melanoma who had either undergone surgical resection of high-risk disease (cohort B) or were receiving or had received medical therapy for advanced disease (cohort C). Patients were followed longitudinally with serial ctDNA measurements with contemporaneous radiographic imaging to ascertain times to detection of disease activity and progressive disease, respectively. The sensitivity and specificity of the ctDNA assay were 86.8% and 100%, respectively. Higher tumor burden and visceral metastases were found to be associated with detectable ctDNA. In two patients in cohort A, ctDNA test results revealed a targetable mutation where tumor testing had not; both patients experienced a partial response to targeted therapy. In four of 30 patients with advanced melanoma, ctDNA assessments indicated evidence of melanoma activity that predicted radiographic evidence of disease progression by 8, 14, 25, and 38 weeks, respectively. CtDNA was detectable in three of these four patients coincident with radiographic evaluations that alone were interpreted as showing no evidence of neoplastic disease. Our findings provide evidence for the clinical utility of integrating ctDNA data in managing patients with melanoma in a real-world setting.

Project description:BackgroundLittle research has focused on implementation of electronic Patient Reported Outcomes (e-PROs) for meaningful use in patient management in 'real-world' oncology practices. Our quality improvement collaborative used multi-faceted implementation strategies including audit and feedback, disease-site champions and practice coaching, core training of clinicians in a person-centered clinical method for use of e-PROs in shared treatment planning and patient activation, ongoing educational outreach and shared collaborative learnings to facilitate integration of e-PROs data in multi-sites in Ontario and Quebec, Canada for personalized management of generic and targeted symptoms of pain, fatigue, and emotional distress (depression, anxiety).Patients and methodsWe used a mixed-methods (qualitative and quantitative data) program evaluation design to assess process/implementation outcomes including e-PROs completion rates, acceptability/use from the perspective of patients/clinicians, and patient experience (surveys, qualitative focus groups). We secondarily explored impact on symptom severity, patient activation and healthcare utilization (Ontario sites only) comparing a pre/post population cohort not exposed/exposed to our implementation intervention using Mann Whitney U tests. We hypothesized that the iPEHOC intervention would result in a reduction in symptom severity, healthcare utilization, and higher patient activation. We also identified key implementation strategies that sites perceived as most valuable to uptake and any barriers.ResultsOver 6000 patients completed e-PROs, with sites reaching 51%-95% population completion rates depending on initial readiness. e-PROs were acceptable to patients for communicating symptoms (76%) and by clinicians for treatment planning (80%). Patient experience was better than the provincial average. Compared to the pre-population, we observed a significant reduction in levels of anxiety (p = 0.008), higher levels of patient activation (p = 0.045), and reduced hospitalization rates (12.3% not exposed vs 10.1% exposed, p = 0.034). A pre/post population trend towards significance for reduced emergency department visit rates (14.8% not exposed vs 12.8% exposed, p = 0.081) was also noted.ConclusionThis large-scale pragmatic quality improvement project demonstrates the impact of implementation strategies and a collaborative improvement approach on acceptability of using PROs in clinical practice and their potential for reducing anxiety and healthcare utilization; and improving patient experience and patient activation when implemented in 'real-world' multi-site oncology practices.

Dataset Information

Personalized Treatment Selection and Disease Monitoring Using Circulating Tumor DNA Profiling in Real-World Cancer Patient Management.

Publications

Personalized Treatment Selection and Disease Monitoring Using Circulating Tumor DNA Profiling in Real-World Cancer Patient Management.

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