Colon Cancer Success Story: Tom (age 65)

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Patient Presentation: Stage IV Colon Cancer

Tom was a 65-year-old man with metastatic stage IV colon cancer from British Columbia, Canada. His cancer had progressed after surgery and chemotherapy. Unfortunately, Tom developed toxicities after eight cycles of oxaliplatin, Avastin, and 5-FU. This resulted in a loss of vision in one of his eyes. The drug combination also produced additional general side effects that Tom had to endure.

Tom then completed another six cycles of avastin/5-FU. He was told by his doctor that he had an excellent response to chemotherapy. Nine months after beginning treatment, Tom had a CT scan done. The scan indicated that the nodes in his liver had responded to therapy: the nodes had decreased in size since his first CT scan, prior to treatment. At this time, his surgeon advised him that the liver nodes were most likely too small for surgery. So instead, they’d wait and see, for the time being.

But Tom didn’t feel comfortable leaving his health up to chance. Instead of just waiting to see what the cancer would do, he reached out to CTOAM for a second opinion

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Colon Cancer Success Story

How CTOAM Helped Tom

1. Interim Support and Personalized Research

First, we reviewed Tom’s medical records and prescribed treatment protocols (both past and present). Our care team then arranged for Tom to work with an independent community oncologist near his hometown. This oncologist was supportive of precision oncology. He also shared CTOAM’s philosophy of working within the medical system as much as possible to meet his patients’ needs.

Our cancer research and patient advocacy experts also encouraged Tom to ask his treatment team to reconsider liver surgery. This recommendation was based on scientific data that demonstrated significant 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. We sent it for tumour DNA sequencing to identify any targetable cancer-causing mutations. This data is essential to determining the most beneficial treatment options for Tom’s unique form of cancer.

• Read more about tumour DNA sequencing

3. Interim Treatment Support

The results from Tom’s tumour DNA sequencing results revealed several mutations that were likely driving his cancer to grow.

Tom’s mutations:

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

• FLT4, p53, and MAPK2
  Tom also had mutations in his FLT4, p53, and MAPK2 genes. Significantly, Tom had two separate mutations in his APC gene. Human beings have two copies of each gene, in case one gets mutated. So the fact that two mutations were found in Tom’s APC gene indicated that both copies of his APC gene were mutated – as opposed to having two separate mutations in a single gene.) However, this is highly unlikely.
  
  This, then, 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. 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 radiofrequency ablation to treat his liver tumors.

• Chemoembolization (CE): This is where 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.
• Radiofrequency ablation (RFA): A surgical technique that uses radio waves to heat up a tumour and destroy it.

4. Monitoring During Treatment

Our cancer research and patient advocacy experts wanted to know the status of Tom’s tumours well before his surgery. So prior to his surgery, we facilitated a liquid biopsy to detect the level of Tom’s KRAS mutation.

• Liquid biopsy: A liquid biopsy detects the tumour DNA based on specific mutations unique to that patient. This is possible because tumour cells leak their DNA into the blood, where it remains stable for some time.

• Read more about liquid biopsies

Measuring Tom’s Mutations

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

• Before surgery: Prior to his surgery, Tom’s KRAS G12V mutation level was 0.2%.
• After surgery: Post-surgery, we performed another ctDNA liquid biopsy. This was to ensure that Tom’s tumours had indeed been ablated and that he did not have recurrence. Surprisingly, the KRAS G12V mutation level in Tom’s body was still high at 0.16%. This indicated that he had a significant amount of cancer in his body.

We urged Tom’s treatment team to do a PET/CT scan to confirm this data. The British Columbia Cancer Agency (BCCA; Tom’s local cancer agency) provided PET/CT a month later. This scan showed new sites of metastasis in Tom’s 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.

CTOAM’s specialists 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. Since Tom had two such mutations, this was not likely to be helpful for Tom.
• Only 12% of patients with KRAS mutations responded to irinotecan.
• 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
• 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.

Tom’s doctors also proposed a second option: selective internal radiation therapy (SIRT) using Yttrium-90 internal radiation therapy for treatment of colorectal cancer liver metastases.

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. So we contacted the makers of SIRT. Fortunately, we concluded that the treatment would not affect Tom’s eligibility for future clinical trials.

Tumour Tissue DNA Sequencing for Cancer Treatment

Additionally, the SIRT procedure would provide us with a fresh sample of the tumours that had metastasized to the liver. It was likely that Tom’s new tumours would have new genetic alterations. Since the sequencing technology had dramatically improved over the previous year, we’d now be able to look at a much larger selection of genes.

After Tom’s SIRT, we had the new tumour tissue sequenced using a comprehensive tumor 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 lapatinib would be effective. We also looked at the MSI and PD-1R/L status of his tumours to determine if the newer immunotherapy PD-1 inhibitors (nivolumab; pembrolizumab) would be effective.

Unfortunately, all tests came back negative. A month after SIRT, Tom had another CT scan, which showed progression of disease in his lungs and liver. Sadly, Tom’s doctors gave him a few months to live.

Finding Effective Cancer Treatment

However, the comprehensive tumor DNA sequencing test had given us a better idea of the molecular basis of Tom’s cancer. This enabled CTOAM to identify a new drug that had recently been shown to be beneficial for some people with advanced colon cancers.

CTOAM’s research identified a multiple kinase inhibitor called regorafenib. There was a recent study of regorafenib in colon cancer patients who’d failed all other options. This study showed that the drug (regorafenib) 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 six to eighteen 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 these findings and recommendations in a report and presented it to Tom’s treatment team. Tom started on regorafenib soon after.

Liquid Biopsy for Cancer Treatment Monitoring

Prior to Tom starting regorafenib, we facilitated a KRAS liquid biopsy (ctDNA). This would act as a baseline tumour burden to ensure the drug was working. The level of KRAS mutations in Tom’s blood (prior to starting regorafenib) was 4.09% – the highest we’d seen in awhile.

One month after Tom has been on the drug, a second ctDNA test was performed. The results showed us that the regorafenib was indeed working: the level of KRAS mutations had dropped from 4.09% to 3.05% – a reduction in 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. He needed many breaks and dose reductions.

Five months after treatment, a CT scan indicated possible further progression in the lung metastasis. We immediately requested that Tom’s doctors provide him with a PET/CT scan funded by the British Columbia Cancer Agency (BCCA).

Cancer Misdiagnosis in Standard Treatment

One month later, CTOAM received the PET/CT scan (funded by BCCA). The scan showed that some of the tumours in Tom’s lungs had grown slightly. Unfortunately, it also showed that one tumour had reached a whopping 11cm in size.

His doctors were shocked. They immediately suggested hospice and a cessation of his regorafenib. To put it plainly, they wanted to stop treatment and place Tom in palliative care. However, CTOAM’s cancer research and patient advocacy experts were skeptical. First, the report did not indicate any invasion of this massive tumour into the lining that surrounds Tom’s lungs. Secondly, Tom himself claimed he had no symptoms such as coughing, blood, or loss of breath.

So we concluded that the 11cm tumour was actually just a typo – and that the tumour was actually a 1.1cm in size. We contacted his treatment team to ask to confirm this. We also requested that they take steps to ensure this egregious error in reporting a test result would not happen again.

Tackling the Real Problem

In any case, the real problem remained that Tom was now unable to tolerate a therapeutic dose of regorafenib. At this point he’d already been on the drug for over 6 months and the side effects were now too damaging to his liver. We needed to find further treatment options.

5. Clinical Trial Support

Our research identified two protocols for Tom:

1. The NEXIRI protocol: A combination of drugs called that resulted in a disease control rate (DCR) of 65% and an overall survival rate of seventh months in heavily pretreated KRAS-mutated colorectal cancer patients.
2. TAS-102: A drug that 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 one-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 (TAS-102) 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. After a few weeks, we 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. Sadly, he died within a month.

How Precision Oncology Helps

Learning From Tom’s Story

Tom’s type of cancer had an obvious inherited component, as well as a combination of molecular alterations that resulted in a very short survival rate. However, he did survive much longer with CTOAM’s services/ctoam-approach/ than he would have with standard treatment. Had Tom listened to his original doctor’s advice, he would have missed out on nearly three years more with his family.

While we always 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. This means you get more quality time with the people you love.

Conclusions

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 research and patient advocacy experts will ensure that you have access to the most advanced tests and treatments available for your unique form of cancer – as close to home as possible.

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