Why Biopsy Is the Key to Personalized Medicine

Alda Tam, MDBiopsy is the foundation of cancer care, but its importance is often understated. As the framework of precision medicine becomes more ingrained in the standard of care, interventional radiologists must remain well versed on the latest advances in biomarker science and be able to communicate with others on the cancer team. In this Q&A, Alda Tam, MD, comments on the current role of biopsy, as well as opportunities for innovation in the near future. Dr. Tam is an interventional radiologist at M.D. Anderson Cancer Center in Houston, Texas and presented on biopsy in personalized medicine on Sunday, February 4 at the Symposium on Clinical Interventional Oncology.

How will biopsy contribute to the future of cancer care?

Dr. Tam: Biomarker-driven cancer care is already important, and it is unlikely that future developments in cancer therapy will deviate from this care paradigm. The ability to discern the genetic make-up and immunological profile of an individual’s tumor is a cornerstone of research and will eventually become the standard of care across many solid malignancies.

What role will liquid biopsy play in the near future?

Dr. Tam: There has been a lot of excitement and speculation around liquid biopsy and when it will replace the image-guided biopsy. Liquid biopsy involves drawing a small amount of blood and using it to determine the genetic profile of the tumor. It’s a less invasive method of analysis when compared to biopsy, and many feel it addresses the issue of tumor heterogeneity because it includes DNA fragments that are shed from all areas of the tumor. The overall idea of liquid biopsy is that you can get all the answers you would get with a typical biopsy but in a less invasive and ultimately less expensive manner. It has been proposed as a tool to monitor response and resistance to therapy, as well as to direct targeted therapy. However, the technology for liquid biopsy is still emerging, and one big drawback is that it cannot provide any insights into the tumor microenvironment, which is an area of great interest for researchers in immuno-oncology.

What are some innovation opportunities in image-guided biopsy?

Dr. Tam: We’ve been performing image-guided biopsy for decades with minimal changes to the equipment design. There haven’t been significant developments in terms of biopsy needles; most are straight, rigid, and either forward-firing or side-cutting for the core biopsy needles.

This represents an innovation opportunity. Some of the projects in biomechanical engineering involving steerable needle tips and different sampling tips are particularly promising and beyond what we currently have to work with. For those who may think that the time of innovation in interventional radiology has passed, this shows that there are still opportunities for invention and innovation.

What are some other opportunities for innovation?

Dr. Tam: Another important area of research that could have a big impact on how biopsy is performed is the integration of point-of-care testing into the workflow. If we had the capability for real-time assessment of a biopsy specimen at the time of tissue acquisition, that would be a real game changer.

What are some of the challenges surrounding the need for a sufficient sample?

Dr. Tam: Currently, approximately 10% to 15% of patients won’t have sufficient material to use for next-generation sequencing tests. Most large trials in which biopsy plays an integral role for randomization to treatment have come across this challenge, which then prompts a discussion on biospecimen adequacy. Standardizing how tissue is acquired would be an important step to meeting this challenge, but this wouldn’t be sufficient in itself given that the landscape of pathology testing is rapidly changing and each trial has its own unique testing requirements. This means that tissue requirements are constantly changing, too.

Until some of the innovation we have discussed regarding biopsy equipment hits the market, the interventional radiologist must take on the responsibility as a clinical trial collaborator to make sure that the tissue requirements “desired” in the protocol are actually acquirable and that a patient has suitable lesion that can be sampled aggressively. We’ve had some protocols that have asked for the acquisition of multiple 14-gauge cores irrespective of organ system. Communicating the expectations to the referring clinical team can help to temper expectations, identify when biopsy is not safe, and guide the prioritization of testing for the tissue that can be acquired.

Do you have any tips for improving communication?

Dr. Tam: In my group, we have specific instruction sheets that are attached to each protocol so all interventional radiologists know the type (FNA or core) and number of biopsy specimens needed. This has helped us to achieve high compliance rates with acquiring the samples needed for individual trials. We do the due diligence of reviewing the lesion prior to the procedure and talking to the oncologist if it appears that the patient does not have a lesion that is likely to yield for molecular testing. Often, if we think there is a chance that the biopsy may be insufficient, we will also have a conversation with the patient during the informed consent process to make sure that they are aware of the challenges. Being evaluated for and entering a clinical trial is usually a very stressful time for patients, and they look at the biopsy as the step that can make or break their shot at a trial spot. Usually these patients have had to stop treatment to ensure an appropriate time for therapeutic washout. They undergo the biopsy and have to wait 1 to 2 weeks for the result. A nondiagnostic biopsy result can then set a patient back for an additional 2 to 3 weeks as they try to find another trial or undergo repeat biopsy, which can be an extremely frustrating experience.

What would you like colleagues to do differently in the area of biopsy?

Dr. Tam: Realize that biopsies aren’t boring! And that getting enough tissue for only histology is no longer adequate. Interventional radiologists are important members of the clinical trial team and should get involved in the clinical decision making for these patients. Biospecimen adequacy is an incredibly important topic, and we will need to address the identified gaps in care as quickly as possible. ν