Genomics is poised to become a major force in cancer care, and therapy guided by genetics is being embraced within established strategies for the treatment of a number of malignancies.
However, in order for this field to expand, standards for acquiring appropriate tissue samples to conduct comprehensive genomic analyses also must evolve, say the authors of a new study. A number of challenges and issues need to be addressed in order to move both the pathology and oncology communities toward a new practice of incorporating larger tissue samples, write the authors of a Viewpoint published in the January 2 issue of Journal of the American Medical Association.
Currently, cancer regimens can be adjusted when mutations such as in the BRAF gene in melanoma or the HER2 gene in breast cancer can be identified.
However, these mutations are only the tip of "an enormous iceberg," because it has become increasingly clear that there are thousands of somatic genomic changes that occur in a large number of solid adult tumors, the authors point out. In addition, the critical driver mutations and biologic pathways can also be determined in many patients, they add.
However, to uncover driver and passenger mutations and to more completely analyze tumor heterogeneity, tissue samples may be need to be larger than they are in the current era of performing less invasive procedures and procuring smaller amounts of tissue.
Research suggests that freshly frozen tumor tissue may provide an expanded capability for more comprehensive genomic sequencing, including RNA sequencing and epigenomic profiling, which can detect methylation and histone modifications. Currently, the standard practice is formalin fixation of tissue.
Coauthor Eric J. Topol, MD, director of the Scripps Translational Science Institute and chief academic officer for Scripps Health, La Jolla, California, feels that many patients would be amenable to having more extensive biopsies performed. Dr. Topol is also editor-in-chief of Medscape Genomic Medicine and Theheart.org.
"This is a really hot area, but the problem is the patients don't know about this," he said in an interview. "We invariably are contacted by patients and even their physicians asking for our help because the patient is not responding to the therapy."
Often all that is available is formalin-fixed, paraffin-embedded (ffp) tissue blocks, which cannot be adequately sequenced, he said.
Dr. Topol notes that there is much resistance from pathologists, in that it would be expensive to have fresh frozen specimens because it requires increased space, monitoring, and electricity for storage in freezers, there would be problems with reimbursement, and so on. "Basically, every excuse under the sun," he said. "But if it was one of them having a new diagnosis of cancer, they would probably like to have as much information as possible."
The other trend is the move to fine-needle aspirates, which are less invasive and may lower the risk of biopsy-related complications but which also yield smaller tissue samples. "The pendulum has swung away from where we need to be — which is to get adequate tissue not only for ffp but for frozen tissue for sequencing," Dr. Topol said.
"So we really have 2 big trends to buck here. Our hope is that pathologists will be responsive, and if patients demand that part of their tissue has to be frozen, their demand has to be honored," he said.
Although some of these issues have not yet been tested, such as a patient demanding frozen tissue and a pathologist refusing to abide by those wishes, "nonetheless, we are moving in this direction," explained Dr. Topol. "We need to call out patients, consumers, patient advocates to be knowledgeable about this, because they are the ones who can drive it."
"Unfortunately, the vast majority of patients are unaware of the opportunity to have a precision diagnosis of driver mutations," he added. "It is really notable that these noninvasive techniques are really noninformative."
The issue of taking larger tissue samples and performing more extensive biopsies has not yet been studied from the patient perspective, note Dr. Topol and coauthors. To date, no prospective studies have been conducted, and they point out that the "critical question is whether more tissue leads to more genetic information that alters care and improves patient outcome."
"But ultimately, if there are trials as we call out for in our paper, then the hope that there will be studies to bear out that this is the right approach, and maybe the evidence base and the consumer demand together will help move us in the right direction," said Dr. Topol.
The authors have disclosed no relevant financial relationships.
JAMA. 2013;309:37-38. Abstract
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Cite this: New Standards of Practice Needed in Cancer Tissue Sampling - Medscape - Jan 02, 2013.