Anastasia’s Story

The Case of Anastasia 

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Patient Presentation

Anastasia was a 69 year old woman from BC, Canada, with a previous history of breast cancer, who had recently been treated for squamous cell carcinoma of the esophagus with chemo and radiation therapy, until her disease had progressed.

Since she had endured previous treatment for breast cancer, surgery, and multiple rounds of chemotherapy and radiation therapy, and since her cancer was progressing on the standard treatments, she was considered palliative and was told to get her affairs in order.

Anastasia wasn’t ready to just accept this and so she reached out to us.

How We Helped Anastasia Using Our 4-Step System

1. Introduced Advanced Diagnostics

Firstly, we 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 who we had experience working with, and suggested that she get a PET/CT to establish the exact state of her disease.

PET/CT, unlike other forms of medical imaging, 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!

Furthermore, 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.

2. Conducted Patient Specific Research

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.

In order 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.

Our research allowed us to focus on Anastasia’s fibroblast growth factor receptor 1 and 2 (FGFR1/FGFR2) amplifications as the most optimal candidates. 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.

Furthermore, our research uncovered additional 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 for us because 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 is 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’.

Based on the multiple alterations in her FGFR signalling pathway, we theorized that Anastasia’s tumour was addicted to FGFR1/2 signalling and that the best course of action would be for her to participate in a clinical trial using a pan-FGFR inhibitor.

3. Interim Treatment Support

We searched the clinical trial databases and identified a variety of trials for both squamous esophagus cancer and cancer patients with FGFR alterations.

Since Anastasia was not enthusiastic about travelling in her condition, we focused on oral medications so that she could participate in a trial with a minimal amount of travel, so that she could do it while staying at home for the most part.

Our research identified the drug BGJ398, a pan-FGFR inhibitor (able to inhibit both FGFR1 and FGFR2) that had substantial data showing its efficacy and effectiveness in this tumour model.

We then contacted the Canadian arm of the drug company that makes BGJ398, and 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 as we now had a combination of drugs that could target multiple signalling mechanisms in Anastasia’s cancer.

Unfortunately, the trial coordinator of this centre did not accept her for this trial.

We then looked at trials in the USA and identified a clinical trial in the USA for BGJ398. We contacted the trial coordinators and Anastasia was accepted into the American trial.

4. Clinical Trial Support and Advocacy

After being accepted into the trial, Anastasia went to the USA 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 and she was told that she did not have a visual tumour, which was required for the trial.

We immediately contacted the trial centre and provided them with previous PET/CT imaging showing her tumour. However, since the radiologist was not experienced with using or reading PET/CTs, our request fell on deaf ears, and Anastasia was sent home feeling dejected and depressed.

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, and 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.

Just to ensure that the drug was working at the low and intermittent dosing, we had her get another PET/CT.

Amazingly, when this PET/CT was compared with one taken 5 months ago, her highly aggressive tumour had not grown at all and the only change was a slight increase in the SUV value from 7.9 to 9.0!

Outcome

Unfortunately, Anastasia decided that she would not seek further treatment, and she died a few months after being taken off votrient.

Had we been able to connect with Anastasia at an earlier date, we might have been able to control the course of her disease 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; the patient’s organs are damaged from years of standard therapies and disease, are taking many medications, and are much harder to treat. While we typically are able to find advanced treatments for our patients, some of them are just too sick for further treatments.

Additional Implications of This Case

On a side note, Anastasia’s tumour DNA sequencing uncovered a rare BRCA2 mutation that was reported as having unknown clinical significance, and therefore, not considered actionable.

We performed computer modelling on this mutation and determined that it was an obviously detrimental mutation that could have played a role in her breast cancer. Although this test does not determine if 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 more than likely inherited.

Should Anastasia’s family members choose to determine if they also carry this mutation, it would only require a simple cheek swab/blood test and a minimal expense.

Conclusions

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