Testing for Tumor Mutations: Liquid Biopsy Versus Traditional Biopsy


Liquid biopsies, virtually unknown even a year or two ago, are becoming common tools in precision diagnostics for cancer. Here, I will try to explain some of the more important differences between liquid and “traditional” tumor biopsies.

Biopsies of solid tumors (e.g., lung, breast, or brain tumors) involve surgically removing a small part of a tumor and sending it to pathology lab. In the last few years, doctors have also started to send some tumor samples to special service labs that analyze tumor DNA for the presence of cancer-related mutations.

By definition, regular biopsies can be intrusive and are sometimes associated with side effects, such as bleeding or infection. However, they provide some really essential information; i.e., the histology and grade of the tumor and other tumor characteristics necessary to determine the best choice of treatment. For lung cancer, for example, a biopsy determines the type of tumor—adenocarcinoma, squamous cancer, small-cell lung cancer, or another, less common type. For breast cancer, a routine test will determine if the tumor expresses estrogen, progesterone receptors, and a protein called HER2. These tests are critically important in guiding treatment choices. If mutational analysis of cancer-related genes is also performed (which doesn’t always happen, unfortunately), it may guide treatment with targeted drugs. Continue reading…


Biodesix Launches GeneStrat Targeted Liquid Biopsy Mutation Test For Patients With Advanced Lung Cancer

“Biodesix, Inc. today announced the launch of GeneStrat™, a targeted liquid biopsy mutation test for genotyping tumors of patients with advanced non-small cell lung cancer (NSCLC). The blood test results are available within 72 hours, providing physicians actionable diagnostic information prior to making treatment decisions. GeneStrat is focused exclusively on the clinically actionable EGFR, KRAS, and BRAF mutations often used to guide targeted therapy treatment decisions. GeneStrat also captures the EGFR T790M mutation, which can be used for monitoring the emergence of the primary resistance mutation in the EGFR gene. It is anticipated that two drugs targeting the resistance mutation may be available later this year. GeneStrat uses the ddPCR platform to analyze cell-free tumor DNA and is highly concordant with tissue analysis, currently considered the gold standard.

“Roughly 30% of lung cancer patients either have insufficient biopsy tissue or are not candidates for a biopsy for tumor mutation profiling. Even in cases where tissue biopsy is available, the sense of urgency to treat is great, with one recent study showing that one out of four patients begin cancer treatment before receiving mutation test results. Requiring only a blood draw, GeneStrat offers a fast, minimally invasive alternative to a high-risk tissue biopsy or re-biopsy in patients with insufficient tissue.

“In addition to providing a minimally-invasive source of mutation status, liquid biopsy can be more cost-effective than traditional tissue biopsies. The mean cost of each tissue biopsy is $14,634 across all patients. The cost of a tissue biopsy can be up to four time higher in the 19.3% of patients who have complications associated with the biopsy. GeneStrat liquid biopsy can help avoid the cost and complications of repeat tissue biopsy.”


DNA Shed by Tumors Shows Promise for Non-Invasive Screening and Prognosis

“Certain fragments of DNA shed by tumors into the bloodstream can potentially be used to non-invasively screen for early-stage cancers, monitor responses to treatment and help explain why some cancers are resistant to therapies, according to results of an international study led by Johns Hopkins Kimmel Cancer Center investigators.

“Analyzing blood samples from 640 patients with various cancers, the researchers used digital polymerase chain reaction-based technology (a sophisticated method of multiplying and measuring the number DNA molecules) to evaluate how well the DNA fragments predicted the presence of tumors in the patients.”


DNA Shed by Tumors Shows Promise for Non-Invasive Screening and Prognosis

“Certain fragments of DNA shed by tumors into the bloodstream can potentially be used to non-invasively screen for early-stage cancers, monitor responses to treatment and help explain why some cancers are resistant to therapies, according to results of an international study led by Johns Hopkins Kimmel Cancer Center investigators.

“Analyzing blood samples from 640 patients with various cancers, the researchers used digital polymerase chain reaction-based technology (a sophisticated method of multiplying and measuring the number DNA molecules) to evaluate how well the DNA fragments predicted the presence of tumors in the patients.”


DNA Shed by Tumors Shows Promise for Non-Invasive Screening and Prognosis

“Certain fragments of DNA shed by tumors into the bloodstream can potentially be used to non-invasively screen for early-stage cancers, monitor responses to treatment and help explain why some cancers are resistant to therapies, according to results of an international study led by Johns Hopkins Kimmel Cancer Center investigators.

“Analyzing blood samples from 640 patients with various cancers, the researchers used digital polymerase chain reaction-based technology (a sophisticated method of multiplying and measuring the number DNA molecules) to evaluate how well the DNA fragments predicted the presence of tumors in the patients.”


Phase II Trial (BREAK-2) of the BRAF Inhibitor Dabrafenib (GSK2118436) in Patients With Metastatic Melanoma

“Purpose: Dabrafenib (GSK2118436) is a potent inhibitor of mutated BRAF kinase. Our multicenter, single-arm, phase II study assessed the safety and clinical activity of dabrafenib in BRAFV600E/K mutation–positive metastatic melanoma (mut+ MM). Patients and Methods: Histologically confirmed patients with stage IV BRAFV600E/Kmut+ MM received oral dabrafenib 150 mg twice daily until disease progression, death, or unacceptable adverse events (AEs). The primary end point was investigator-assessed overall response rate in BRAFV600E mut+ MM patients. Secondary end points included progression-free survival (PFS) and overall survival (OS). Exploratory objectives included the comparison of BRAF mutation status between tumor-specific circulating cell-free DNA (cfDNA) and tumor tissue, and the evaluation of cfDNA as a predictor of clinical outcome…Conclusion: Dabrafenib was well tolerated and clinically active in patients withBRAFV600E/K mut+ MM. cfDNA may be a useful prognostic and response marker in future studies.”