I’ve been concerned about the practice of next-generation sequencing (NGS), especially about what information is generated and how it will be used. Thus, a colleague suggested that I read Being Mortal: Medicine and What Matters in the End by Atul Gawande, M.D.,1 since the book deals with what humans want, especially from cancer diagnosis and therapy. One looming problem is that NGS can give definitive diagnosis of the mutations responsible for a patient’s cancer. But today’s state of knowledge is so low that NGS will discover many different cancers before treatment is available. It is the nature of science that one generally looks for causes after the disease is isolated and characterized. Thus, there will probably always be a cohort of afflicted before successful therapy is worked out.
Dying is part of living. How we live and die is our story. Dr. Gawande points out that the American way of treating serious illness is inconsistent with human values. He does this with a series of stories reporting the decline of several patients, including his father, who was also an MD. This is a very effective way of presenting the decision-making process in treating cancer.
Next-generation sequencing is expected to characterize cancers by their genetic mutation as opposed to their location. Eric Topol has pointed out that, “It’s the mutation, not the location!” But what will we do with the information?
If the diagnosis of mutation leads to connection with a therapeutic, as is the case with companion drugs such a herceptin, this is the best one can hope for. Certainly even better theranostic pairs will be developed. But this takes time.
What to do with the results from NGS for which the companion therapy has not been developed? The answer seems to depend upon the stakeholder. The treating physician faces a dilemma. He or she has a patient with a disease that has no likely cure. What can be done? If the mutation is known, then the doctor can look for a clinical trial. Perhaps there is a reputable therapy developed outside the U.S.A. Or, the physician can propose a generalized “Hail Mary” therapy of radiation plus chemotherapy, as vividly described by Dr. Gawande. These make the patient sick with a long list of unpleasant symptoms including nausea, weakness, loss of appetite, incontinence, and on and on. For what? The oncologist is trying to extend life. The oncologist is looking for an extension of months, while the patient is hoping for as many years. This is a fundamental disconnect.
While reading, I repeatedly flashed back on our two Golden Retrievers. We were uniquely responsible for playing God by managing their end-of-life treatment. Both died recently from cancer. The male bled to death halfway through chemotherapy for hemangiosarcoma. His last months after initial diagnosis were not pleasant for him and certainly not for us. Two years later, his sister developed bone cancer, leading to amputation of a front leg at the shoulder. “Tri Paw” lasted only thee excruciating months after the amputation. We wonder still what we had done to our beloved dogs. We felt that we tortured them because we hoped that the best available technology might give them more time with us. This is similar to the pressure that the medical community puts on patients when they propose heroic treatment plans. By nature and training, they want to help while hoping for a miracle.
We felt we had to give our dogs a chance, but the force was not with them. Would we do it again? I think not. It is not the money but the agonizing death we saw them endure. And if we would not do it to the next dog, then is there a lesson there for treating humans? After all, life is about the loving of pets as wells as friends and family. My reading of Dr. Gawande’s book is that we get trapped with wanting to do something, almost anything, in hopes of a miracle. Others may accept their fate. Family members apparently talked the senior Dr. Gawande out of taking this trail. He finally had to say “enough!” Would I be strong enough to resist? Time may tell.
So back to the main thread. NGS will certainly give information to help categorize cancers by their mutation, location, and treatment attempts. Hopefully, treatments that do not work will be recorded as will successes. I’m sure the present system will provide a steady stream of desperate, very ill patients who will want to try any clinical trial. This information should be curated into databases that can be used by researchers and healthcare providers to winnow opportunities from ineffective therapies.
This means that it is in the public interest for NGS to report all data collected for each patient, even variants of unknown significance (VUS). Data mining will probably be essential to discovering new therapeutic approaches. Many VUS will not be significant, but some will show a pattern that may lead to an effective therapy and life extension with quality. Quality of life should be a key criterion, and the patient should be the judge—the sole judge. Dr. Gawande points out that, in the end, it is the person who needs to optimize his path depending upon his own values.
It’s no surprise that Being Mortal tops The New York Times bestsellers list. It is a must read for every adult.
Reference
- Gawande, A. Being Mortal: Medicine and What Matters in the End. Metropolitan Books, 2014; ISBN 978-0-8050-9515-9.
Robert L. Stevenson, Ph.D., is Editor, American Laboratory/Labcompare; e-mail:[email protected].