Blood Samples Analysis Monitors Colorectal Cancer Chemotherapy Response
By LabMedica International staff writers Posted on 18 Nov 2015 |
Circulating cell-free DNA (cfDNA) may be collected from plasma of colorectal cancer patients and represents a less invasive, less costly approach to tracking biomarkers of interest longitudinally and at progression.
Paired tumor biopsies obtained prior to a given targeted therapy and following progression may inform on dynamic genetic changes which drive resistance; however, these procedures are expensive and associated with risk to colorectal cancer patients.
Scientists at the MD Anderson Cancer Center (Houston, TX, USA) and their colleagues enrolled patients with refractory B-Raf proto-oncogene, serine/threonine kinase (BRAF)-mutated metastatic colorectal cancer (mCRC) onto a phase I clinical trial of vemurafenib with irinotecan and cetuximab. Restaging scans to assess response to treatment were performed every eight weeks using RECIST 1.1 criteria. Serial plasma samples were collected at treatment initiation, prior to each scheduled dose, and following progression.
Circulating cell-free DNA (cfDNA) was extracted from plasma and analyzed using droplet digital polymerase chain reaction (ddPCR, Bio-Rad; Hercules, CA, USA) to quantify the fraction of mutant BRAFV600E allele relative to BRAF wild-type allele. The cfDNA collected from pretreatment and post-progression plasma samples were analyzed via next-generation sequencing (NGS) using a 68-gene panel (Guardant Health; Redwood City, CA, USA) to identify copy number changes and novel acquired mutations present at progression. Of 19 patients enrolled in the study, serial plasma samples were available for 12.
The median number of plasma samples per patient was 9.5 (range 3 to12). Among the six patients with partial responses radiographically, the median reduction from baseline of BRAFV600E allele was -98% two weeks after treatment initiation. For those with stable disease, the median change was -33%, which was significant when compared to those with partial responses. cfDNA was increasing at the time of progression in all patients (9/9) and preceded progression in 67% (6/9). Novel MEK1C121S, ARAFS490T, and GNASR201C mutations, not identified at baseline, were present at progression. Confirming the digital PCR methodology, NGS identified increased allelic frequency in BRAFV600E, neurofibromatosis type 1 (NF1), and adenomatous polyposis coli (APC) at disease progression.
Van Morris, MD, an assistant professor and lead author of the study said, “BRAF V600E mutations were present in circulating cell-free DNA from all 12 patients in the study for whom serial plasma samples were available, and the direction of change in the ratio of BRAF V600E to BRAF wild-type appeared to correlate with whether or not a tumor responded to treatment. Declines in the ratio preceded detection of a radiographic response and increases, following an initial response, were observed before a radiographic progression.” The study was presented at the International Conference on Molecular Targets and Cancer Therapeutics, held November 5–9, 2015 in Boston (MA, USA).
Related Links:
MD Anderson Cancer Center
Bio-Rad
Guardant Health
Paired tumor biopsies obtained prior to a given targeted therapy and following progression may inform on dynamic genetic changes which drive resistance; however, these procedures are expensive and associated with risk to colorectal cancer patients.
Scientists at the MD Anderson Cancer Center (Houston, TX, USA) and their colleagues enrolled patients with refractory B-Raf proto-oncogene, serine/threonine kinase (BRAF)-mutated metastatic colorectal cancer (mCRC) onto a phase I clinical trial of vemurafenib with irinotecan and cetuximab. Restaging scans to assess response to treatment were performed every eight weeks using RECIST 1.1 criteria. Serial plasma samples were collected at treatment initiation, prior to each scheduled dose, and following progression.
Circulating cell-free DNA (cfDNA) was extracted from plasma and analyzed using droplet digital polymerase chain reaction (ddPCR, Bio-Rad; Hercules, CA, USA) to quantify the fraction of mutant BRAFV600E allele relative to BRAF wild-type allele. The cfDNA collected from pretreatment and post-progression plasma samples were analyzed via next-generation sequencing (NGS) using a 68-gene panel (Guardant Health; Redwood City, CA, USA) to identify copy number changes and novel acquired mutations present at progression. Of 19 patients enrolled in the study, serial plasma samples were available for 12.
The median number of plasma samples per patient was 9.5 (range 3 to12). Among the six patients with partial responses radiographically, the median reduction from baseline of BRAFV600E allele was -98% two weeks after treatment initiation. For those with stable disease, the median change was -33%, which was significant when compared to those with partial responses. cfDNA was increasing at the time of progression in all patients (9/9) and preceded progression in 67% (6/9). Novel MEK1C121S, ARAFS490T, and GNASR201C mutations, not identified at baseline, were present at progression. Confirming the digital PCR methodology, NGS identified increased allelic frequency in BRAFV600E, neurofibromatosis type 1 (NF1), and adenomatous polyposis coli (APC) at disease progression.
Van Morris, MD, an assistant professor and lead author of the study said, “BRAF V600E mutations were present in circulating cell-free DNA from all 12 patients in the study for whom serial plasma samples were available, and the direction of change in the ratio of BRAF V600E to BRAF wild-type appeared to correlate with whether or not a tumor responded to treatment. Declines in the ratio preceded detection of a radiographic response and increases, following an initial response, were observed before a radiographic progression.” The study was presented at the International Conference on Molecular Targets and Cancer Therapeutics, held November 5–9, 2015 in Boston (MA, USA).
Related Links:
MD Anderson Cancer Center
Bio-Rad
Guardant Health
Read the full article by registering today, it's FREE!
Register now for FREE to LabMedica.com and get complete access to news and events that shape the world of Clinical Laboratory Medicine.
- Free digital version edition of LabMedica International sent by email on regular basis
- Free print version of LabMedica International magazine (available only outside USA and Canada).
- Free and unlimited access to back issues of LabMedica International in digital format
- Free LabMedica International Newsletter sent every week containing the latest news
- Free breaking news sent via email
- Free access to Events Calendar
- Free access to LinkXpress new product services
- REGISTRATION IS FREE AND EASY!
Sign in: Registered website members
Sign in: Registered magazine subscribers
Latest Pathology News
- AI Integrated With Optical Imaging Technology Enables Rapid Intraoperative Diagnosis
- HPV Self-Collection Solution Improves Access to Cervical Cancer Testing
- Hyperspectral Dark-Field Microscopy Enables Rapid and Accurate Identification of Cancerous Tissues
- AI Advancements Enable Leap into 3D Pathology
- New Blood Test Device Modeled on Leeches to Help Diagnose Malaria
- Robotic Blood Drawing Device to Revolutionize Sample Collection for Diagnostic Testing
- Use of DICOM Images for Pathology Diagnostics Marks Significant Step towards Standardization
- First of Its Kind Universal Tool to Revolutionize Sample Collection for Diagnostic Tests
- AI-Powered Digital Imaging System to Revolutionize Cancer Diagnosis
- New Mycobacterium Tuberculosis Panel to Support Real-Time Surveillance and Combat Antimicrobial Resistance
- New Method Offers Sustainable Approach to Universal Metabolic Cancer Diagnosis
- Spatial Tissue Analysis Identifies Patterns Associated With Ovarian Cancer Relapse
- Unique Hand-Warming Technology Supports High-Quality Fingertip Blood Sample Collection
- Image-Based AI Shows Promise for Parasite Detection in Digitized Stool Samples
- Deep Learning Powered AI Algorithms Improve Skin Cancer Diagnostic Accuracy
- Microfluidic Device for Cancer Detection Precisely Separates Tumor Entities