This is the first blog I have penned since COVID-19 swept through the country. So troubling were the consequences of the pandemic that I felt my pieces should not distract from the gravity of the situation. As we now slowly return to normal life, I thought it time might be time to re-open a dialogue. Those of you who watch television might recognize a commercial with a talking dog. It opens with a woman bringing her boxer to the veterinarian. The doctor inquires “So what’s going on?” and the dog replies “I’m a talking dog”. The owner admonishes her pet saying “No; the other issue” and the dog replies “Oh…. I’m scratching like crazy”. At this point, the owner and doctor take up treatments for dog rash, seemingly oblivious to the input from their canine interlocutor. This reminds me of a patient who was the subject of a February 2020 blog.
In March of 2019, he traveled from Des Moines, Iowa to Houston, Texas to receive care at a major cancer center for his newly diagnosed metastatic gastroesophageal cancer. When he did not respond to first line therapy, the Texas group offered standard second-line therapy. Fearing that further guideline-driven chemo might again prove ineffective, he traveled to California to undergo a biopsy for an EVA/PCD assay that revealed an unexpected combination.
A Genetic Clue
The Houston center had conducted a DNA (genomic) test and found a minor mutation in a gene that drives many colon cancers, known as the epidermal growth factor receptor or EGFR. The gene profile described the patient’s EGFR mutation as a variant of uncertain significance (VUS). This term is applied when a gene mutation is not considered responsible for the cancer’s growth. From a therapy standpoint, VUS genes are not considered “actionable”, meaning that drugs used to target them aren’t likely to work.
Most academic centers dismiss VUS as irrelevant. However, in this patient’s laboratory study, we found a very high level of activity for drugs that targeted his EGFR-mutation indicating that his EGFR variant was very significant. We used the laboratory findings to craft a combination of therapy that worked almost immediately. My February blog marveled at his good outcome as measured both by tumor markers and PET scans. Writing today, I’ve just gotten off the phone with the patient and his wife after we reviewed his most recent PET/CT. Astonishingly, the PET/CT showed no evidence of active disease in the esophagus where it began or in the neck where our original biopsy had been obtained For background, the combination of chemotherapy that we recommended worked extremely well but after several cycles of treatment the patient did suffer the common drug related nerve injury known as neuropathy that can occur with this class of drugs.
A Second Novel Cocktail Works Even Better
Rather than guessing how to modify treatments to avoid further neuropathy, our EVA/PCD results allowed us to craft a new combination that worked equally well but did not cause neuropathy.
I had not kept in close touch with the patient, but did call on June 5th to commemorate the one-year anniversary of our first meeting. Today’s call was much more exuberant, as we explained the remarkably good results.
During his treatment the patient had developed an allergic reaction to the drug Carboplatin and was being considered for a desensitization protocol. Desensitization uses slowly escalating doses to achieve drug tolerance and can be very successful, but it requires an intensive care unit. The Chicago center where he was receiving care did not offer desensitization so he approached the University of Iowa.
Say What?
What was surprising was the university-based physician’s response.
Here was a patient who 15 months earlier had been given a death sentence by an internationally recognized cancer center. This now healthy 60-year-old man in complete remission who had benefited from not one but two highly effective drug combinations both crafted from his own tumor. These were combinations that absolutely no one else would ever have given him.
In the face of this miraculous outcome, the UI physician said, “Well, maybe we can just observe you”.
What? No attaboys, words of congratulation, or admission that his remission was fully two standard deviations removed from anyone’s wildest dream. Not a word of praise or support, just “Move along, nothing to see here”. Here was an academic physician who could not see the forest for the tree. He was “blinded by science”. Had I been in this situation no matter who had provided the care, I would have complimented the patient on his good outcome and commented on the unusual nature of the treatment. But this physician was not about to admit that a laboratory-guided combination had worked. Instead, he needed to take control. All that had occurred before their meeting at the university hospital was nothing but a chance event. It was his expertise that would matter now. Moving Forward The patient’s reaction was the same as mine. As a result, he hasn’t sought further opinions from that medical center. We, at this point will modify doses and schedules to provide a simple maintenance program going forward. In addition, we can now begin to use the word cure in our discussions; no guarantees of course but the hope thereof. We could not be happier for this gentleman’s good outcome. It is in its own way a miracle. I did however encourage the patient to follow up with the Iowa University doctor as I very much wanted this physician to be introduced to my talking dog.
As always, I appreciate your thoughts and comments.