The Case of Mark – Esophageal squamous-cell carcinoma
Mark is a 53 year man from BC, Canada whom was recently diagnosed with stage IV esophageal squamous-cell carcinoma. A CT scan provided to him by his public system oncologist found a significant mass in his esophageal-stomach junction, with possible metastasis to the liver.
This was not a surprise as Mark was a heavy smoker, had a very poor diet, and had been unable to keep food down for some time. In fact, he had lost so much weight that he was unable to do even the most basic physical activities.
Although standard chemotherapy would have only been able to provide him with a year or two survival, Mark’s doctors told him that since there was the potential of liver metastasis, treatment with standard chemotherapy was not an option for him.
Mark’s oncologists suggested that he get low dose palliative radiation therapy and told him to get his affairs in order.
Mark was not willing to accept this outcome so, he reached out to us for a second opinion and to access some advanced diagnostic and treatment technologies which are not yet available via the public medical system.
How We Helped Mark Using Our 5-step System
1. Introduced Advanced Diagnostics
Firstly, since the potential of chemotherapy would be based on whether he had metastasis or not, we arranged for a private PET-CT from a local clinic that we work with called Premier Diagnostic center.
This clinic is our first choice for PET-CT’s because we get results very quickly, it is one of the lowest costing scans we know of, and the radiologist reports the SUV values of EVERY tumor, unlike many other clinics we have dealt with.
It is very important that PET-CT is done prior to any treatments as tumors are often missed when they are at a point that they could easily be removed.
This is because PET-CT, which unlike other forms of medical imaging, is able to identify active tumors at a very small size, based on the biological activity of the tumor.
While most forms of imaging look at the density of the tumor and compare it to the surrounding tissues, PET-CT uses a harmless radioactive isotope that is bound to a sugar molecule.
Since tumor cells are constantly growing and therefore highly metabolic, they drink up more of the sugar-isotope solution than the surrounding tissues and any tumors will glow like Christmas tree lights.
Importantly, since only live tumors will drink the sugar-isotope solution, PET-CT can tell if a tumor is alive or if it has been affected (killed) by a specific treatment. No other form of imaging can reveal this essential information!
Furthermore, since the amount of the sugar-isotope solution a specific tumor drinks depends on how fast it is growing, a PET-CT can determine how aggressive a specific tumor is compared with other tumors in the body. This is referred to as the serum uptake value (SUV), and allow doctors to focus on the tumors that are most likely to metastasize.
Unfortunately the PET-CT showed that Mark’s had a massive 6.4cm tumor in his esophageal-stomach junction that had an SUV = 8.5, and additional metastasis in his liver.
Secondly, we had Mark contact a local oncologist whom was prepared to offer Mark off-label targeted drugs should the scientific evidence indicate a benefit.
A word about targeted therapies
Standard chemotherapy drugs work by inhibiting any rapidly reproducing cells in the body. Typically, these drugs interfere with a cell’s ability to replicate; however, they are not specific to cancer cells and will kill ANY cell that happens to be reproducing during treatment.
This unfortunately, results in many harsh and permanent side effects.
Furthermore, standard chemotherapy drugs do not typically target the actual cancer-causing stem cells that create the bulk of the tumors, as these unique cells are resistant to standard chemotherapy.
Targeted drugs work by targeting genetic or molecular alterations that are ONLY found in your tumor cells, and do typically affect your normal healthy cells.
2. Conducted Patient Specific Research
In order to determine if Mark’s tumors contained any targetable mutations, we obtained a sample of his tumors and conducted an extensive panel of tests including tumor DNA sequencing and HER2 testing.
Tumor DNA sequencing looks at a variety of targetable genetic mutations in the DNA of tumor cells, and HER2 is a targetable molecular feature common to breast cancers that has recently been found in certain stomach cancers. Patients that have high HER2 respond well to the drug Herceptin.
Unfortunately, the tumor DNA sequencing did not reveal any known targetable alterations and all of his mutations were unknown and unique to him.
While this is not a common occurrence for us, we can still use the unknown genetic mutations to perform an analysis using computer-based modeling.
Our computer based modelling indicated that Mark’s tumor more than likely would respond to a certain class of drugs called programmed death one (PD-1) immune checkpoint inhibitors.
A word on PD-1 and checkpoint inhibitors
The PD-1 protein is found on the surface all body cells and tells our immune system that the cell is part of our body and NOT a foreign invader. Some tumors escape being attacked by our immune system by producing massive amounts of PD-1 protein and in doing so, form protective blankets around themselves.
PD-1 inhibitors work by acting like a sponges and soaking up any excessive PD-1. This allows the immune system to recognize the tumors, often resulting in massive and durable responses against the cancers cells.
It is thought that once the immune system has been disabled by the PD-1 blanket that surround a particular tumor, then it does not return again to the same sight as it views any further tumor-like activity as a false alarm. In other words, all tumors will at one time express PD-1, but will do so at different times during the course of the disease.
Additionally, we found that diet and exercise had a strong role in reducing the growth potential of this specific metabolic based tumor, so we created a tumor fighting diet and exercise plan for Mark, which he followed faithfully.
3. Interim Treatment Support
Since our computer modelling indicated that Mark would potentially respond to PD-1 inhibitors, we performed a PD-1 ctRNA liquid biopsy blood test. This test measures the amount of PD-1 protein. The higher the level, the better the response to these drugs is.
While most commercial PD-1 tests examine the amount of PD-1 from a single biopsy sample, ctRNA measures the amount of PD-1 body wide. This is important because as previously noted, not all tumors in the body will produce the immune disabling PD-1 blanket at the same time.
Since the liquid biopsy detects circulating PD-1 protein (ctRNA) body-wide, it provides us with a rough idea of the total amount of PD-1 ligand produced by all of Mark’s cancer cells.
The liquid biopsy test showed us that Mark’s PD-1 protein levels were over 10.4 times higher than the normal body levels, indicating the potential for a significant response from PD-1 inhibitors.
We immediately shared this information with Mark’s new oncologist, and he arranged for immediate infusions of the PD-1 inhibitor drug pembrolizumab.
4. Testing During Treatment
After a few treatments with pembrolizumab, Mark reported feeling much better. His body weight started to improve and as his tumor markers started to drop.
Importantly, a PET-CT showed a decrease in the SUV of his stomach tumor, going from 8.55 prior to treatment, down to SUV = 4.
This reduction in tumor activity allowed Mark to have his feeding tube replaced with a stent. Remarkably, when the surgeon put in his stent, he could find no evidence of the massive 6.5 cm tumor that was previously blocking his esophagus.
5. Clinical Trial Support and Advocacy
After reviewing the latest gastrointestinal conferences, we gathered new research showing that when patients with esophagus cancers were given a drug called a MEK inhibitor (trametinib), these patients responded to much better to PD-1 inhibitors.
In fact, our initial computer modelling analysis also indicated that a MEK inhibitor could potentially help Mark. It is thought that in certain genetic backgrounds, the MEK inhibitor stimulates an immune response.
Pembrolizumab and Trametinib
We presented this new plan to Mark’s and his treatment team and this combination will be considered should he progress.
Recently, Mark reported that he has gained another 24 pounds since his last infusion.
Although his recent PET-CT did show an increase in liver metastasis, we believe this is a false positive result, which is common with immune therapies as they stimulate the immune cells to enter the tumors, making them appear much larger initially when imaged.
However, this initial false positive response is typically followed by a reduction in SUV values, indicating a less active tumor.
Importantly, when patients respond to PD-1 inhibitors, the responses are very durable and we have seen many cases where even after 2-3 treatments, the tumors never came back.
We do hope this is the case with Mark, and will be updating this report in the near future.
As you can see, CTOAM’s advanced diagnostics, records review and consultations can result in significant benefits to a patient’s outcome.
Having access to a team of knowledgeable scientists, doctors and patient advocates that WORK FOR YOU and NOT THE MEDICAL SYSTEM, can make all the difference in the outcome of your disease!
If you or a loved one is fighting cancer, give us a call so we can do a brief review of your medical records. It is important to be sure that you KNOW that you are doing all you can, and that you have access to the best treatments for your own unique case. (778) 999-5463