Carcinoma Success Story: Anastasia (age 69)
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Patient Presentation: Squamous Cell Carcinoma of the Esophagus
Anastasia was a 69-year-old woman from British Columbia, Canada. She had a previous history of breast cancer. She’d also been recently treated for squamous cell carcinoma of the esophagus with chemotherapy and radiation therapy. Unfortunately her disease had progressed and she was unable to continue those therapies.
To summarize: Anastasia had endured previous treatment for breast cancer, as well as undergone surgery, multiple rounds of both chemotherapy and radiation therapy, and her cancer was progressing despite these standard treatments. Her doctors considered her palliative; she was told to get her affairs in order.
However, Anastasia wasn’t ready to accept this. So she reached out to CTOAM for help.
Carcinoma Success Story
How CTOAM Helped Anastasia
Firstly, our cancer experts obtained a sample of Anastasia’s tumour tissue and sent it for tumour DNA sequencing. We looked for cancer-causing mutations in the DNA of over 340 genes involved in cancers.
Secondly, we asked Anastasia to contact an independent community oncologist near her home town (whom we’d had prior positive experience working with). We suggested that she get a PET/CT scan immediately to establish the exact state of her disease.
What is a PET/CT Scan?
Unlike other forms of medical imaging, a PET/CT scan is able to identify active tumours at a very small size, based on the biological activity of the tumour. While most forms of imaging look at the density of the tumour and compare it to the surrounding tissues, PET/CT uses a harmless radioactive isotope that is bound to a sugar molecule. Since tumour cells are constantly growing and therefore highly metabolic, they drink up more of the sugar-isotope solution than the surrounding tissues and any tumour will glow like a Christmas tree light.
Since only live tumours will drink the sugar-isotope solution, PET/CT can tell if a tumour is alive or if it has been affected (killed) by a specific treatment. No other form of imaging can reveal this essential information!
Further, since the amount of the sugar-isotope solution a specific tumour drinks depends on how fast it is growing, a PET/CT can determine how aggressive a specific tumour is compared with other tumours in the body. This can allow doctors to focus on the tumours that are most likely to metastasize.
Anastasia’s DNA sequencing results indicated that her cancer had a variety of genetic mutations that could indicate sensitivities to specific drugs that targeted these mutations.
To determine the best possible targets for treatment, we researched numerous previous cases and databases for genetic variables known to drive the development of squamous cell carcinomas of the esophagus.
CTOAM’s research allowed us to focus on Anastasia’s fibroblast growth factor receptor 1 and 2 (FGFR1/FGFR2) amplifications as the most optimal candidates.
Understanding Cancer Treatment
What is a Gene Amplification?
Gene amplification: A gene amplification is a common alteration in cancers and results in multiple copies of a specific gene that plays a role in cancer growth and development.
When gene amplifications occur, the result is an increase in the product of the gene compared to what is required by the cell under normal conditions. In the case of amplification, even a small amount of the fibroblast growth factor would result in a massive amount of unregulated growth (cancer).
While alterations in one of the FGFR genes is common in squamous carcinomas of the esophagus, Anastasia actually had two FGFR genes amplified, resulting in a hyper-sensitivity to this signalling pathway.
Our research further uncovered more data showing that when patients with FGFR1 alteration also have high levels of a protein called MYC, they were much more sensitive to drugs that inhibit FGFR1 than when MYC is not found at a high level.
This was exciting news! Anastasia also had an amplification of her MYC gene, which would have led to high levels of this protein, resulting in what is referred to as oncogene addiction.
- Oncogene addiction: The concept that a specific cancer is dependent on a key signalling pathway, and that any disruption of this pathway would result in substantial tumour death. In this case, the FGFR/MYC mutations could result in a molecular Achilles heel (so to speak).
Based on the multiple alterations in her FGFR signalling pathway, we theorized that Anastasia’s tumour was addicted to FGFR1/2 signalling. Therefore, the best course of action would be for her to participate in a clinical trial using a pan-FGFR inhibitor.
We searched the clinical trial databases and identified a variety of trials for both squamous esophagus cancer and cancer patients with FGFR alterations.
- Finding a trial close to home:
Understandably, Anastasia was not keen to travel in her condition. Therefore, we focused on finding a clinical trial that used oral medications so she could participate while staying at home (for the most part).
- Finding the right drug:
Our research identified the drug BGJ398, a pan-FGFR inhibitor (able to inhibit both FGFR1 and FGFR2). This drug had substantial data showing its efficacy and effectiveness in this tumour model.
- Corresponding with the trial:
CTOAM’s care team then contacted the Canadian arm of the drug company that makes BGJ398. They provided us with a Canadian clinical trial that was offering BGJ398 in combination with another drug that also targeted another one of Anastasia’s mutations (PTEN). This was a serendipitous finding: we now had a combination of drugs that could target multiple signalling mechanisms in Anastasia’s cancer.
- Applying to the trial:
Unfortunately, the trial coordinator of this centre did not accept her for this trial.
- Getting accepted:
We then looked at trials in America and found one for BGJ398. Our care team contacted the trial coordinators – and, happily, Anastasia was accepted into this American trial.
After being accepted into the trial, Anastasia went to America to start her new treatment regime.
While there, a radiologist decided to do a CT scan of her tumour. Unfortunately, this new CT scan could not find her tumour. Anastasia was told she didn’t have a visual tumour, which was required for the trial.
CTOAM immediately contacted the trial centre and provided them with previous PET/CT imaging that clearly showed her tumour. However, the radiologist (from the clinical trial) was not experienced with using or reading PET/CT scans. Our request was ignored and Anastasia was sent home feeling dejected.
We then researched the British Columbia Cancer Agency’s (BCCA) treatment guidelines for FGFR inhibitors and identified a drug called votrient. At the time, votrient was approved for renal cell cancers but it also worked in part by inhibiting FGFR1 and FGFR2 signalling.
We immediately wrote up a patient report for Anastasia’s health care treatment team, and her community oncologist was able to prescribe her votrient.
During the course of her treatment, Anastasia was not able to tolerate the full dose of votrient. She required frequent treatment interruptions and some dose reductions that prevented the drug from working to its full potential. This was not surprising as she was in poor health by now, and had a multitude of other conditions that required medication.
To ensure that the drug was working at the low and intermittent dosing, we asked her to get another PET/CT scan.
Incredibly, the new PET/CT revealed that her highly aggressive tumour had not grown at all – when compared with the PET/CT taken five months prior. In fact, the only change was a slight increase in the SUV value from 7.9 to 9.0. This was great news.
5. Patient OutcomeUnfortunately, Anastasia decided that she would not seek further treatment. Sadly, she died a few months after being taken off votrient. Had CTOAM been able to work with Anastasia at an earlier date in her disease’s progression, we might have been able to control the course of her disease. This may have been possible using different FGFR targeted drugs, or by targeting some of the other genetic mutations identified in her tumour DNA sequencing panel. Unfortunately, most of our patients come to us at a very late stage of disease when the individual tumours’ cells have significant genetic diversity. At that point, the patient’s organs are often damaged from years of standard therapies and disease. They’re also usually taking many medications and, in general, are much harder to treat. While we’re typically able to find effective targeted treatments for our patients, some of them are just too sick for further treatments.
Genetic Impact of Cancer on Families
Can Colon Cancer be Inherited?
An important side note: Anastasia’s tumour DNA sequencing uncovered a rare BRCA2 mutation that was reported as having unknown clinical significance. Therefore, it was not considered actionable.
We performed computer modelling on this mutation. From this modelling, we were able to determine that it was an obviously detrimental mutation that could have played a role in her breast cancer. Although this test does not determine whether this is an inherited (familial) or non-inherited (occurs only in the tumour – somatic), recent data concluded that, like many other BRCA mutations, this specific mutation results in a slightly increased risk of breast and ovarian cancers, and is most likely inherited.
If Anastasia’s family members want to know whether they also carry this mutation, all they’d need to do is get a simple, inexpensive cheek swab or blood test.
As you can see, CTOAM’s advanced diagnostics, records review, and consultations can result in significant benefits to a patient’s outcome. In this case, precision oncology allowed Tom to outlive the average person with his genetic predisposition and survive two years and eight months from his original diagnosis. Having access to a team of precision oncology specialists, doctors, and patient advocates can make all the difference in both the length and quality of time you have with your loved ones.
If you or a loved one has cancer, contact us today so we can do a brief review of your medical records. CTOAM’s cancer experts will ensure that you have access to the most advanced tests and treatments available for your unique form of cancer – for as close to free, and as close to home, as possible.
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