Pharmacokinetic Tumor Heterogeneity as a Prognostic Biomarker for Classifying Breast Cancer Recurrence Risk

Mahrooghy, Majid; Ashraf, Ahmed Bilal; Daye, Dania; McDonald, Elizabeth S.; Rosen, Mark; Mies, Carolyn; Feldman, Michael D.; Kontos, Despina

doi:10.1109/tbme.2015.2395812

Cited by 50 publications

(38 citation statements)

References 36 publications

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“…Because molecular heterogeneity has also been associated with poor patient outcome (42, 43), we next sought to assess the prognostic significance of ctDNA molecular heterogeneity. For the 98 patients with metastatic disease, the median overall survival from time of metastatic diagnosis in patients with ≥3 variants detected in plasma was 46 months versus 62 months for those with <3 variants, although this result did not reach statistical significance (p=0.09; Figure 4A).…”

Section: Resultsmentioning

confidence: 99%

Detection of Therapeutically Targetable Driver and Resistance Mutations in Lung Cancer Patients by Next-Generation Sequencing of Cell-Free Circulating Tumor DNA

Thompson

Yee

Troxel

et al. 2016

Clinical Cancer Research

278

242

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Purpose The expanding number of targeted therapeutics for non-small cell lung cancer (NSCLC) necessitates real-time tumor genotyping, yet tissue biopsies are difficult to perform serially and often yield inadequate DNA for next-generation sequencing (NGS). We evaluated the feasibility of using cell-free circulating tumor DNA (ctDNA) NGS as a complement or alternative to tissue NGS. Experimental Design 112 plasma samples obtained from a consecutive study of 102 prospectively enrolled patients with advanced NSCLC were subjected to ultra-deep sequencing of up to 70 genes and matched with tissue samples, when possible. Results We detected 275 alterations in 45 genes, and at least one alteration in the ctDNA for 86 of 102 patients (84%), with EGFR variants being most common. ctDNA NGS detected 50 driver and 12 resistance mutations, and mutations in 22 additional genes for which experimental therapies, including clinical trials, are available. While ctDNA NGS was completed for 102 consecutive patients, tissue sequencing was only successful for 50 patients (49%). Actionable EGFR mutations were detected in 24 tissue and 19 ctDNA samples, yielding concordance of 79%, with a shorter time interval between tissue and blood collection associated with increased concordance (p=0.038). ctDNA sequencing identified 8 patients harboring a resistance mutation who developed progressive disease while on targeted therapy, and for whom tissue sequencing wasn’t possible. Conclusions Therapeutically targetable driver and resistance mutations can be detected by ctDNA NGS, even when tissue is unavailable, thus allowing more accurate diagnosis, improved patient management, and serial sampling to monitor disease progression and clonal evolution.

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Section: Resultsmentioning

confidence: 99%

Detection of Therapeutically Targetable Driver and Resistance Mutations in Lung Cancer Patients by Next-Generation Sequencing of Cell-Free Circulating Tumor DNA

Thompson

Yee

Troxel

et al. 2016

Clinical Cancer Research

278

242

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“…[1][2][3][4] Recently, computer algorithms have been applied to automatically extract large numbers of quantitative features that thoroughly describe various characteristics of tumors and their surroundings. These features have been applied to the determination of patient diagnosis, 5,6 prognosis of outcomes, [7][8][9][10] and for their association with genomics. [11][12][13][14] These analyses are currently referred to as radiomics 15 and radiogenomics.…”

Section: Introductionmentioning

confidence: 99%

Breast cancer MRI radiomics: An overview of algorithmic features and impact of inter‐reader variability in annotating tumors

2018

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“…Breast cancer MRI features have also been correlated with clinically available genomic assays (OncotypeDx, Genomic Health, CA; MammaPrint, Agendia, CA; Mammostrat Clarient Diagnostic Services, CA; PAM50/Prosigna NanoString, WA), which provide scores to predict recurrence and guide treatment decisions. 100,103,[121][122][123] Ashraf et al investigated radiogenomic correlations of DCE-MRI features and the 21-gene recurrence score assay OncotypeDx. 122,124 They were able to identify four dominant imaging phenotypes, two of which were exclusively associated with low-and cancer.…”

Section: Recurrence Scoresmentioning

confidence: 99%

Background, current role, and potential applications of radiogenomics

Pinker

Shitano

Sala

et al. 2017

Magnetic Resonance Imaging

152

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Pharmacokinetic Tumor Heterogeneity as a Prognostic Biomarker for Classifying Breast Cancer Recurrence Risk

Abstract: HetWave could be a powerful feature extraction approach for characterizing tumor heterogeneity, providing valuable prognostic information.

Cited by 50 publications

References 36 publications

Detection of Therapeutically Targetable Driver and Resistance Mutations in Lung Cancer Patients by Next-Generation Sequencing of Cell-Free Circulating Tumor DNA

Detection of Therapeutically Targetable Driver and Resistance Mutations in Lung Cancer Patients by Next-Generation Sequencing of Cell-Free Circulating Tumor DNA

Breast cancer MRI radiomics: An overview of algorithmic features and impact of inter‐reader variability in annotating tumors

Background, current role, and potential applications of radiogenomics

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