Tom’s Story

The Case of Tom – Stage IV Colon Cancer

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Tom’s History

Tom was a 65 year old man with metastatic stage IV colon cancer from British Columbia, Canada, who had progressed after surgery and chemotherapy. Unfortunately, after 8 cycles of oxaliplatin, Avastin, and 5-FU, Tom developed toxicities that resulted in a loss of vision in one of his eyes, along with the general negative side effects from taking this drug combination.

Tom then completed another 6 cycles of avastin/5-FU and he was told that he had an excellent response to chemotherapy. A CT scan taken 9 months after he began treatment indicated that the nodes in his liver had responded to therapy and had decreased in size since his first CT scan (prior to treatment).  At this time, his surgeon advised him that the liver nodes were more than likely too small for surgery and that they would wait and see for the time being.

Tom wasn’t comfortable just ‘waiting and seeing’ what the cancer would do so he reached out to us to ensure he was doing all that he could do.

How We Helped Tom Using Our 5-Step System

1. Interim support/initial personalized research

First, we reviewed Tom’s medical records and past and currently prescribed treatment protocols.

Then we arranged for Tom to work with an independent community oncologist near his hometown who we know is supportive of both precision oncology and working as much within the medical system as possible to meet the needs of his patients.

We also suggested that Tom contact his treatment team and ask them to reconsider liver surgery given the scientific data on the benefits of this surgery in cases like Tom’s.

2. Introduced advanced diagnostics

Next, we obtained a sample of Tom’s tumour tissue from an existing tissue biopsy and sent it for tumour DNA sequencing for the purpose of identifying any targetable cancer causing mutations for Tom’s treatment plan.

3.  Interim Treatment Support

The results from Tom’s tumour DNA sequencing results showed that he had a few mutations that were likely driving his cancer to grow.

The KRAS G12V mutation, which was present for Tom, is a negative prognostic feature. Patients with this mutation have minimal response to chemotherapy with a median progression free survival (PFS) of about 9.5 months, with most patients living less than 2 years. Furthermore, this mutation also prevents the use of the FDA approved EGFR targeted drugs.

Tom also had mutations in in his FLT4, p53, and MAPK2 genes. Importantly, Tom had two separate mutations in his APC gene. Since we have two copies of each gene (in case one gets mutated), the fact that two mutations were found in Tom’s APC gene indicated that both copies of his APC gene were mutated (rather than having two separate mutations in a single gene), which is highly unlikely.

This indicated that Tom was born with a genetic defect in one copy of his APC gene, and that over time, the other copy of his APC was also mutated, resulting in his colon cancer. In other words, he had an inherited genetic susceptibility to this cancer.

Unfortunately, this specific combination of genetic mutations results in a very aggressive and highly metastatic form of colon cancer that is unlikely to respond to most standard therapies. We predicted a likely survival time of less than 1.5 years from the time of his initial diagnosis.

After a recent CT scan showed new metastasis in his liver, Tom’s treatment team decided to use chemoembolization and radio frequent ablation to treat his liver tumors.

With chemoembolization (CE), anti-cancer drugs are injected directly into the blood vessels feeding the tumour, while the vessels leaving the tumour are plugged with a gel like substance.

Radio frequency ablation (RFA) is a surgical technique that uses radio waves to heat up a tumour and destroy it.

4. Monitoring During Treatment

In order to ensure that we knew the status of Tom’s tumours well in advance of his surgery, we performed a liquid biopsy to detect the level of Tom’s KRAS mutation prior to his surgery.

Tumour cells leak their DNA into the blood, where it remains stable for some time. A liquid biopsy detects the tumour DNA based on specific mutations unique to that patient.

Since Tom’s KRAS mutation is unique to his tumour cells, we could measure the amount of the KRAS mutation prior to and after a therapy to get an idea of the relative amount of tumour cells in his body. If the treatment is working, we will see a significant decrease in the percentage of the KRAS mutation in a sample of his blood.

Prior to his surgery, his KRAS G12V mutation level was 0.2%.

To ensure that Tom’s tumours had indeed been ablated and that he did not have a recurrence, we performed another ctDNA liquid biopsy post surgery. Surprisingly, the KRAS G12V mutation level in Tom’s body was still high at 0.16%, indicating that he had a significant amount of cancer in his body.

We urged his treatment team to do a PET/CT to confirm this data, and a BCCA provided PET/CT a month later showed new sites of metastasis in his liver and lungs.

Based on his latest imaging showing the potential of new liver and lung metastasis, Tom’s doctors suggested that he be treated with irinotecan based chemotherapy. We then researched the key molecular features that would allow us to predict if Tom’s tumours would be sensitive to irinotecan or not.

Our research showed that colon cancer patients with APC mutations only had a 15% response rate to irinotecan, and Tom had two such mutations. So this was not likely to be helpful for Tom.

Furthermore, only 12% of patients with KRAS mutations responded to irinotecan. And finally, only patients that had a gain of DNA on chromosomes 1q23.3, 1q44, 8p22-23, 19q13.1, or 19q13.2 respond to irinotecan based-chemotherapy, and 0% of patients that DID NOT have the above mentioned chromosomal alterations responded to irinotecan. Tom had gains on chromosomes 13 and 20, so unfortunately, irinitecan would not help him at all.

A second option was proposed by Tom’s doctors:

Selective internal radiation therapy (SIRT) using Yttrium-90 internal radiation therapy for treatment of colorectal cancer liver metastases.

With SIRT, microscopic glass beads containing radioactive Yttrium-90, are injected directly into the liver. While there was not a lot of data on this technique, a few studies had shown that it provided some benefits to certain patients at an early stage of the disease. However, our concern was that the radioactive glass beads actually remained in the body and were not removed, possibly preventing his participation in future clinical trials.

We contacted the makers of SIRT, and concluded that the treatment WOULD NOT affect Tom’s eligibility for future clinical trials.

Additionally, the SIRT procedure would provide us with a fresh sample of the tumours that had metastasized to the liver. Not only was it likely that Tom’s new tumours would have new genetic alterations, but the sequencing technology had dramatically improved over the previous year, and we would now be able to look at a much larger selection of genes.

After Tom’s SIRT, we had the new tumour tissue sequenced using the advanced Foundation One DNA sequencing panel.

We also had Tom’s tumours tested for other molecular features that would allow the use of targeted therapies.

For example, we looked at Tom’s HER2 levels to determine if anti-HER2 therapies such as Herceptin and lapatenib would be effective. We also looked at the MSI and PD-1R/L status of his tumours to determine if the newer immune therapy PD-1 inhibitors nivolumab or pembrolizumab would be effective.

Unfortunately, all tests came back negative, and a CT scan a month after SIRT showed progression of disease in his lungs and liver.

Sadly, Tom’s doctors gave him a few months to live.

However, the F1 test gave us a better idea of the molecular basis of Tom’s cancer and allowed us to identify a new drug that had recently been shown to be beneficial for some people with advanced colon cancers.

Our research identified a multiple kinase inhibitor called regorafenib. A recent study of regorafenib in colon cancer patients who had failed all other options showed that the drug worked for patients with KRAS mutations. Importantly, this drug also targeted some of the mutations that Tom had in his new tumours. Additionally, this drug could potentially provide Tom with another 6-18 months of life.

Furthermore, we identified important prognostic features of this drug showing that patients with high neutrophils, high platelets, low lymphocyte counts, or high neutrophil to lymphocyte ratios (NLR) had a poor response to regorafenib treatment.

We immediately wrote up a report for Tom’s treatment team and he started on regorafenib.

We also did a KRAS liquid biopsy prior to starting regorafenib to act as a baseline tumor burden, so that we could ensure the drug was working. The level of KRAS mutations in Tom’s blood was 4.09%, the highest we had seen in a while.

A second ctDNA test performed after one month on the drug showed us that the regorafenib was indeed working. The level of KRAS mutations had dropped from 4.09% to 3.05%, a reduction of over 25% of the amount of cancer cells in his body.

Unfortunately, one of the side effects that regorafenib has is that it can affect the function of the liver. Since Tom’s liver had be ravaged by cancer and various treatments, it was difficult for him to stay on the required dose and he needed many breaks and dose reductions.

A CT scan 5 months after treatment indicated possible further progression in the lung metastasis. We immediately requested that Tom’s doctors provide him with a BCCA funded PET/CT.

One month later, we were provided with a BCCA PET/CT scan that showed not only had some of the tumours in his lungs grown slightly, but one tumour had reached a whopping 11cm in size. His doctors were shocked and immediately suggested hospice and a cessation of his regorafenib. In other words, they wanted to stop treatment and place Tom in palliative care.

Furthermore, the report did not indicate any invasion of this massive tumour into the lining that surrounds Tom’s lungs.  And finally, Tom himself claimed he had no symptoms such as coughing, blood, or loss of breath.

We concluded that the 11cm tumour was actually a typo and that the tumour was a 1.1cm tumour. We contacted his treatment team and asked that they confirm this was the case – and to take steps to ensure this significant an error in reporting a test result does not occur again!

The real problem was that since Tom had now been on regorafenib for over 6 months, he was not able to tolerate a therapeutic dose, so we needed to find further treatment options that did not affect his liver.

5. Clinical Trial Support.

Our research identified two protocols:

1 – A combination of drugs called the NEXIRI protocol that resulted in a disease control rate (DCR) of 65% and an overall survival rate of 7 months in heavily pretreated KRAS-mutated colorectal cancer patients.

2 – A drug called TAS-102, which was an oral combination of trifluridine with tipiracil hydrochloride (an agent that blocks the metabolism of trifluridine). A study in patients with metastatic colorectal cancer refractory/intolerant to standard therapies resulted in a median survival rate of 7.2 months and a 1 year survival rate of 27.1%. A retrospective analysis of this trial in patients over 65 years showed a disease control rate of 48.7%.

Importantly, this drug did not affect the liver in the same way that regorafenib and the NIXIRI protocol did.

We immediately contacted Tom’s private oncologist. Unfortunately, the drug was not available in Canada, so we contacted the distributors of the drug, and after a few weeks, were able to have them honour a prescription written by Tom’s private Canadian oncologist.

Unfortunately, Tom was not deemed healthy enough for further treatment and he died within a month.

How Tom’s case can help you

Tom’s type of cancer had an obvious inherited component, and a combination of molecular alterations that result in a very short survival rate. However, he did outlive the average person with his genetic predisposition and survived 2 years and 8 months from his original diagnosis.

While we all hope that remission will be the end result for all cancer patients, sometimes our genes are stacked against us. Even in cases like Tom’s, we can still use leading edge science and targeted treatments to prolong life expectancy and to reduce the experience of treatment side effects, meaning you get more true quality time with the people you love.

Remember, cancer is unique to every person. Your genetics and your lifestyle will create a unique combination of treatment options. Make sure you are doing all you can to beat cancer.

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Call our Cancer Care Team at (778) 999-5463, or email contact@ctoam.com, for a free initial consultation today.