The below is a transcript from Dr. Eric Topol video, director of the Scripps Translational Science Institute and Editor-in-Chief of Medscape (subscription required). In a series, The Creative Destruction of Medicine, named for a book he wrote, he is trying to zoom in on critical aspects of how the digital world can create better healthcare. Perhaps the most interesting part of his comments are his thoughts on the ever-popular notion in pathology about being able to do more with less – that is more diagnostic and prognostic information with less tissue (i.e. fine needle aspiration cytology and small needle core biopsies from minimally invasive procedures versus open biopsies or surgeries). He claims we need to move away from less and go back to more. Ample tissue specimens for adequacy to assess tumor heterogeneity and have ample tissue not only for paraffin-embedded tissue assays but also flash-frozen specimens for next generation sequencing and other genomics/proteomics downstream. Perhaps this is the way to go. Large tissue volumes with more tumor burden to assess more fields within a tissue and more cells to analyze without destruction of tissue or having to rely on other means because of minimal tissue or lack of additional tissue that could provide answers beyond which we cannot thoroughly evaluate by cytology or small cores alone.
Where will pathologists stand on this issue? Realistically, it probably doesn’t matter what pathologists think – we will likely do what we are told to as is usually the case. Before we had large excisional biopsies and mastectomies and lymph node dissections for grading and staging rather than aspirates and lumpectomies and sentinel lymph nodes. Cytopathologists will likely disagree that more is necessarily more and will continue to pride themselves on doing more (or at least the same) with less and provide preserved cells for downstream analysis. More conservative histomorphologists will relish the idea of having more to do more.
Cancer care is rapidly changing, if we think about where it was some years ago as it was really beautifully archived in a book by Sid Mukherjee, MD, The Emperor of All Maladies,and to where we can go in the future. Just launched recently, for example, was MD Anderson Cancer Center’s Moon Shots program in cancer care. The Moon Shots program is perhaps, because of genomics, digitizing the genome of the tumor, comparing it with the genome-native germ line. This gives us an opportunity we never had before.
So what is the cancer clinic of the future going to look like, because it’s just starting to get developed today? For example, when we have an individual presenting for a new diagnosis of cancer, we have to move away from fine-needle aspiration and minimal tissue; we need real tissue to be able to process it properly. Not only do we need the formalin-fixed paraffin-embedded (FFPE) specimen, but we also need another type of FF — that is, flash-frozen specimens so that we can then whole-genome sequence this tissue.
Now, when that is done at the primary diagnosis and done within hours and analyzed with the appropriate software algorithms, we could get the driver mutations nailed within 24 hours from the diagnosis. This can set up remarkably precise therapy that can be given to the patient on the basis of that individual’s tumor. There are no 2 different cancers that are the same anywhere. Just like there are no 2 individuals who have the same DNA, that’s the same for a tumor.
One of the issues that we have to confront is that there’s a lot of intratumor heterogeneity. We need multiple samples to sequence from the tumor, and if there’s already a metastatic lesion, we need a sample of that as well. Multiple sequencing, frozen tissue, genome-driven guided therapy — right from the get-go — is what we need. That’s not what we have today, but that’s where we can go in the future of cancer genomic medicine. It’s really an exciting opportunity. It has to be validated.
The cancer drugs that are used today are remarkably expensive, and what’s fascinating is to see — and this is a recurrent theme — is that a drug being used, for example, for renal carcinoma can also be used for leukemia. There was a classic 3-part article on the front page of the New York Times that exemplified some of the stories along those lines.
It’s a story about mutations — a war on mutations, not a war on cancer — and this type of cancer clinic in the future can take us there but there’s going to have to be a whole different look with respect to the way that we take samples of the tumor. We need much more tissue, and to use frozen tissue so that we don’t have to bootstrap the FFPE (that paraffin-embedded specimen) and only get a couple of hundred genes or coding elements, but in fact get a whole genome from the flash-frozen specimen. That’s really important, and we have to move in that direction — get more tissue in order to account for the heterogeneity that we know exists. And we have to do deep sequencing of that frozen tissue in order to get the driver mutations identified, and also be able to anticipate where relapses can occur downstream.
That is precision therapy. This exemplifies the future of cancer genomic medicine, and it will be really interesting to see how that plays out in these cancer clinics of the future.