Dr. Robert A. Nagourney, MD
For Medical Oncology, Déjà Vu All Over Again
Yogi Berra said, “It’s like Déjà vu all over again”. I am reminded of this adage following interactions with a group of investigators who have suddenly become very interested in the use of each patient’s tissues to predict chemotherapy response.
After I spoke at this cancer forum, several patients expressed interest in using our EVA/PCD platform to submit tissue from their institutions at the time of surgery.
Unfortunately, neither effort succeeded. In the first, a university hospital in Southern California simply refused to process the sterile tissue for transport. In the second, a patient in South Carolina realized that no matter what we reported, his physicians simply refused to use the recommendations; so much for the Hippocratic Oath!
A subsequent email thread joined by a bevy of researchers and commercial entities all suddenly recognized the difficulty getting samples in an abjectly hostile medical environment. They tearfully bemoaned the fact that their own newfound enthusiasm for human tissue studies to predict response to chemotherapy is not shared by their academic colleagues. Duh!
In fact, they only have themselves to blame.
While dedicated investigators in the US, England, Europe, and Japan labored to conduct these studies over the past three decades, amassing thousands hard-fought analyses in the service of their patients, these now-unhappy investigators have had an epiphany: Chemosenstivity tests work. Yet, it was they and their institutions that denigrated the field and refused to sponsor studies or publish the results.
Like Little Jack Horner, these scientists “Put in a thumb, pulled out a Plumb and said, “Oh what a good boy am I”.
Not so fast. A generation of scientists and clinician has been trained to dismiss even the most compelling data in the field: “None so blind as those who will not see”.
Newcomers to the field are now realizing how difficult it is to convince doctors to use human tissue to study drug response. It is after all a paradigm shift. Surgeons are accustomed to doing surgery only if they can achieve complete remission or to address a life-threatening complication like a bowel obstruction.
Nowhere in the textbook does it recommend removal of a portion of tumor for the express purpose of selecting chemotherapy. Often, when a surgeon is asked to do so, the proverbial “tilt” sign goes off across their eyes and the shut down like a pinball machine that has been treated too roughly.
More than 2 generations of physicians cannot conceive of the value of human tissue for the purpose of drug selection.
To change this will require an extraordinary educational effort. We are now confronting physicians who simply do not get it. They are accustomed to doing biopsies in the form of needle and core, but these are only adequate for molecular studies and immuno-histochemical studies, though sometimes valuable they are insufficient to select drugs.
As the limits of human genomics become increasingly apparent, it is evident that human tissue is the only vehicle by which to predict patient response. After all, if the genomic revolution were indeed remotely what has been touted, then the last two decades would have led to many more curative therapies. Unfortunately, that is not the case.
In fact, human genomics is only the starting point of drug selection. Yes, we can find an occasional patient with an ALK rearrangement, or an EGFR mutation, and these fortunate few do beautifully. However, they are rarely cured, and their recurrences are heralded by increasing aggressive disease.
Despite this, human tissue profiles can continue to provide unique insights into drug response, even if there is no gene rearrangement, splice variant or amplification to target. Cancer biology is, after all, biology and biological measures like human tumor primary culture are the most discriminating of all available tests.
We suggest that patients who are interested in using these approaches contact our office. We will work with them to get the biopsy and if necessary, have them travel to us. We will conduct the surgical procedures working with the team of pathologists who know exactly what to do and how to get us optimal specimens.
Once the results are in hand, it is much easier to find a medical oncologist who will use the results. For those patients whose physicians will not use the right treatment, despite the likelihood of benefit, then we will assume their care for one or two cycles to prove that our recommendations are effective.
Cancer patients must take charge of their disease. They can no longer await a medical community to move at a glacial pace. Cancer moves quickly. Patients must respond and we are here to help them obtain the tissue, identify the treatments and, if necessary, deliver the treatments so they can get the best chance of outcome.