Serial Liquid Biopsies May Predict Response to Colon Cancer Tretment

MedicalResearch.com Interview with:

Andrea Sottoriva, PhD, MSc Reader in Cancer Evolutionary Dynamics | Evolutionary Genomics & Modelling Lab Centre for Evolution and Cancer | The Institute of Cancer Research London

Dr. Sottoriva

Dr. Andrea Sottoriva, PhD
Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom


MedicalResearch.com: What is the background for this study?
Would you briefly explain what is meant by a liquid biopsy?


Response:
Cetuximab is a targeted treatment available for metastatic colorectal cancer patients. Unfortunately, although many patients benefit from Cetuximab, after an initial response to the treatment many patients relapse and become resistant to the drug.

We know that this resistance is due to the tumour evolving and adapting to therapy. Liquid biopsies allow to look for residual cancer DNA in the blood of a patient and hence monitor the emergence of resistance over time. We used blood samples take every 4 weeks (quite frequently for this type of study) to monitor the evolution of the cancers under treatment and see if there were some measurements that would predict if and when patients will relapse.

Continue reading

Liquid Biopsy Using Circulating Tumor DNA Can Predict Treatment Response in Large B-Cell Lymphoma

MedicalResearch.com Interview with:
Dr. David Kurtz, MD/PhD, Instructor and
Dr. Ash Alizadeh MD/PhD, Associate Professor
Division of Oncology, Department of Medicine
Stanford University Medical Center 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: This work investigates the utility of circulating tumor DNA – a type of liquid biopsy – in diffuse large B-cell lymphoma, the most common blood cancer in adults.

Liquid biopsies are an emerging technology to track cancers from a simple blood draw. Here, using a cohort of over 200 patients from 6 centers across North America and Europe, we asked if circulating tumor DNA could be used to detect lymphoma in patients, and more importantly, could it be used to identify responders and non-responders.  Continue reading

Liquid Biopsy for CTCs Can Predict Treatment Response in Advanced Prostate Cancer

MedicalResearch.com Interview with:

Alison L. Allan, PhD Department of Oncology, Western University London Regional Cancer Program, London Health Sciences Centre London, Ontario, Canada 

Dr. Allan

Alison L. Allan, PhD
Department of Oncology, Western University
London Regional Cancer Program, London Health Sciences Centre
London, Ontario, Canada 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: This was an international collaborative study between Lawson Health Research Institute (London, ON), Memorial Sloan Kettering Cancer Center (New York), the Royal Marsden (London, UK) and molecular diagnostics company Epic Sciences (San Diego, CA). The study used a liquid biopsy test developed by Epic Sciences that examines circulating tumour cells (CTCs) in blood samples from patients with advanced prostate cancer who are deciding whether to switch from hormone-targeting therapy to chemotherapy. CTCs are cancer cells that leave a tumour, enter the blood stream and invade other parts of the body, causing the spread of cancer. The test identifies whether or not a patient’s CTCs contain a protein in the nucleus called AR-V7. The research team set out to determine whether the presence of this protein predicted which treatment would best prolong a patient’s life.

They found that patients who tested positive for the protein responded best to taxane-based chemotherapy while those who tested negative for the protein responded best to hormone-targeting therapy with drugs called androgen-receptor signaling (ARS) inhibitors. These are the two most widely used drug classes to treat advanced prostate cancer.

Continue reading

Liquid Biopsy Can Guide Radiation Therapy in Early Stage Breast Cancer

MedicalResearch.com Interview with:

Chelain Goodman, MD PhD PGY-3, Radiation Oncology Northwestern University Chicago, IL 60611

Dr. Goodman

Chelain Goodman, MD PhD
PGY-3, Radiation Oncology
Northwestern University
Chicago, IL 60611

MedicalResearch.com: What is the background for this study?

Response: Circulating tumor cells are cancer cells that are shed from the primary tumor into the peripheral blood stream and are hypothesized to be one of the first steps in the initiation of metastatic progression. Prospective studies have demonstrated that approximately 15-25% of patients with early-stage breast cancer can be found to have at least one circulating tumor cell in a small sample of their blood. Currently, all patients with early-stage invasive breast cancer who undergo breast conserving surgery receive adjuvant radiation therapy. In these analyses, we wanted to determine whether presence of circulating tumor cells may be predictive of benefit of radiation therapy following surgery.

Continue reading

Liquid Biopsy Results for Cancer Mutations May Differ – Study Compares Idylla platform vs to OncoBEAM RAS CRC assay

MedicalResearch.com Interview with:

Dr. Ana Vivancos, Principal Investigator Cancer Genomics Group Vall d'Hebron Institute of Oncology (VHIO Barcelona 

Dr. Ana Vivancos

Dr. Ana Vivancos PhD, Principal Investigator
Cancer Genomics Group
Vall d’Hebron Institute of Oncology (VHIO
Barcelona 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Our study was designed to address a key issue in liquid biopsy testing: analytical sensitivity. We know that mutations in plasma of mCRC patients show a wide range in their allelic frequencies (0.01-90%), the biological basis for which remains unclear. We also know that around 35% of cases show very low mutant allele fractions (MAFs), < 1%, therefore highlighting the need of using high sensitivity techniques in the routine lab in order to properly detect mutations.

We have compared two different testing methods that are being used in liquid biopsy:

Digital PCR (OncoBEAM RAS test, BEAMing) with a limit of detection of 0.02% vs qPCR (Idylla ctKRAS test, Biocartis) with an analytical sensitivity of 1%.

Our findings indicate that detection sensitivity decreases for the qPCR based method in cases with low MAF (<1%) and more so when MAF values are very low (<0.01%).

Continue reading

Liquid Biopsies Sent To Different Labs May Yield Different Results

MedicalResearch.com Interview with:
Gonzalo Torga, MD
Urology Department
Johns Hopkins Hospital
Baltimore, MD 21287

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Liquid biopsy is a new and noninvasive alternative to tumor tissue sequencing, and it is intended to specifically detect and sequence tumor DNA circulating in patients’ blood. The results are used to help guide oncologists to tailor the best treatment for patients at each point of their disease. Our research was initially aimed at finding the best commercial lab to test samples from metastatic prostate cancer patients. We wanted to make the best choice for our patients, so we started submitting the samples to both places at the same time to compare results. However, we found significant disparities in the results from identical patient samples submitted to two different commercial liquid biopsy providers, and we believed it would be important to share them with the oncology community.

The two liquid biopsy panels compared were the Guardant360, from Guardant Health, Inc., which sequenced at least part of the coding sequences of 73 genes; and the PlasmaSELECT panel from Personal Genome Diagnostics, which sequenced coding segments of 64 genes.  Both laboratories were licensed by Clinical Laboratory Improvement Amendments (CLIA) and accredited by the College of American Pathologists (CAP), and report having high sensitivity (in this case, the ability to correctly identify mutations when they occur) and high specificity (the ability to correctly report as negative when those mutations are not present). The two companies differ in which genes, and regions within each gene, are covered. Just 25 of the 40 patients in the study had at least one genetic mutation reported within the overlapping genetic sequences covered by both companies.

Even when the companies were analyzing DNA from the same blood drawn, their results rarely matched each other. When comparing results within the overlapping genetic sequences, the results from both companies completely matched for all the mutations reported in only 7.5 percent (3 of 40 patients) of cases. In 15 percent of the patients (6 of 40), both companies’ results matched for at least one of the reported mutations. In 40 percent (16 of 40) of the patients, no mutations reported that were potentially covered by both panels were detected by both companies.

Continue reading

Penn Reports Successful Pilot Study of Liquid Biopsy To Monitor Advanced Lung Cancer

MedicalResearch.com Interview with:

Erica L. Carpenter, MBA, PhD Research Assistant Professor, Department of Medicine Director, Circulating Tumor Material Laboratory Division of Hematology/Oncology Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania

Dr. Erica Carpenter

Erica L. Carpenter, MBA, PhD
Research Assistant Professor, Department of Medicine
Director, Circulating Tumor Material Laboratory
Division of Hematology/Oncology
Abramson Cancer Center
Perelman School of Medicine at the University of Pennsylvania

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The advent of precision medicine practices for cancer patients, including the use of drugs that target specific tumor mutations, has necessitated improved diagnostics with real-time molecular monitoring of patients’ tumor burden. While biopsy material, obtained surgically or through fine needle aspirate, can provide tissue for next generation sequencing (NGS) and mutation detection, this requires an invasive often painful procedure for the patient. In many cases, especially in more advanced disease when multiple metastases are present, such tissue cannot be obtained or can only be obtained from a single tumor site, thus limiting the sensitivity of tissue-based biopsy.

Here we report on a prospective cohort of 102 consecutively enrolled patients with advanced non-small lung cancer (NSCLC) for whom a non-invasive liquid biopsy was used for real-time detection of therapeutically targetable mutations. Tissue samples were only obtainable for 50 of the 102 patients, and these tissue biopsies were analyzed using a 47-gene Next Generation Sequencing (NGS) panel at Penn’s Center for Personalized Diagnostics. Concordance of results for the 50 patients who received both tests was close to 100% when the samples were obtained concurrently.

Continue reading

New Technology Can Detect Circulating Colon Cancer Cells In Less Than an Hour

MedicalResearch.com Interview with:
Dr. Elodie Sollier PhD
Chief Scientific Officer at Vortex Biosciences

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Vortex Biosciences has developed a fast and simple way to isolate and collect intact circulating tumor cells (CTCs) directly from whole blood in less than an hour using a process based on microfluidics. To better understand the utility of the technology for the clinical setting, PCR-based Sanger sequencing was used to profile the mutations of CTCs isolated from blood from metastatic Colorectal cancer patients. The mutations were compared to primary tumor biopsies, secondary tumor biopsies and ctDNA. There are 3 primary take-aways:

  1. The Vortex technology captures CTCs with enough purity to perform sensitive and accurate PCR-based Sanger sequencing.
  2. Mutations present in primary and secondary tumors can be identified in both CTCs and ctDNA making liquid biopsies a valuable alternative to tissue biopsies.
  3. While there is general consistency of mutations identified, some mutations are only identified in CTCs while others only in ctDNA demonstrating how these are indeed complimentary.

Continue reading