Hello again. Episode 8 will discuss Genetic Testing which can lead to Precision Medicine.

Genetic Testing is relatively new; however, it is potentially a game-changer in your Glioblastoma treatment. The first human genome ever mapped was completed in 2003 and took 13 years to complete and cost up to an estimated 3 billion US dollars. This testing is available today and takes approximately two weeks to complete and costs several thousand dollars. An incredible advancement that has opened the door to the field of Precision Medicine. Where drugs do not target a single type of cancer but instead target specific Oncogenetic drivers across potentially many cancer types. The future of precision medicine is here today. What will likely be considered standard practice in the not-too-distant future is available today. In the January 15, 2022, published European Journal of Human Genetics study the Canadian genetic professionals surveyed believed that by 2030 genetic testing would be broadly implemented. If the experts see the direction towards genetic testing increasing in the near future, we should probably take note and when possible implement tomorrows medicine today to our benefit. In many cases future advances are something we need to await; however, in this case the testing is already available and we can take advantage of what this may offer. We may find no useful information today; but, who knows what possibilities are just around the corner that could be available if we have the genetic testing completed.

What is Genetic testing?

How do I prepare for this testing? Where do I go for this testing? Is Genetic Testing Expensive? What could be found? Why should I do genetic testing of my tumor? We will review each of these questions and more in order to assist you and your medical team in preparing to discuss and review Genetic Testing.

What is Genetic Testing?

Genetic Testing is where the Pathology Department at your hospital or medical facility prepares representative samples of your tumor and ships them to a Laboratory where they conduct genetic testing on your tumor to determine the genetic profile of the tumor, possible Oncogenetic drivers of the tumor and any precision medicine that may be available to treat your cancer. It is important to know that Genes tell cells what to do, including when to make new cells. Additionally, it may also provide possible clinical trials available for patients with your tumor profile and Oncogenetic drivers. Specific qualifications for each trial will be done through a screening process with the clinical trial. There will be a Principle Investigator who will likely be involved with you. They and their team will evaluate each patient and determine if there is a good fit with their Clinical Trial. Additionally, the testing also reveals biomarkers. A
cancer biomarker is a substance or process that is suggestive of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. It could be a protein, a gene, or other molecules. Changes in biomarkers over time can show changes in your cancer that may help you and your medical team. We see that genetic testing includes a genetic profile of the tumor and information about the biomarkers of your cancer. All of this information can be useful to you and your medical team in pursuit of possibilities, viable options, or potentially precision medicine.

How do I prepare for Genetic Testing?

To prepare for Genetic Testing you will need to discuss this with your medical team. Specifically, you will want to discuss this with your oncologist, and neurosurgeon, and ensure your pathologist is contacted. You will let each of them know that you will be having your tumor genetically tested. Typically, this means that the tumor will be taken from the operating room to the pathology department where it will be prepared. This process involves the pathologists determining the best sample to send and then preparing the tumor according to the specifications required by the Laboratory conducting the Genetic Testing. This may involve preparing the sample in paraffin wax, or freezing the sample for future testing availability.

It is important to let your medical team know which laboratory or company you have chosen to do the Genetic Testing. Your Oncologist will typically need to prepare an application. You will need to pay the lab or company you have selected for the testing. And your oncologist will provide the Pathology department with the sample specifications (ensure this is done and who is responsible to identify and retain the samples).

Even if you decide not to test at the moment; you should review this with your medical team so that the sample is prepared for future use. Perhaps, a genetic test of this tumor will be useful in the future.

Where do I go for genetic testing?

There are several choices to have genetic testing completed. I have used two different laboratories including Foundation Medicine and MSK Impact. I preferred the Foundation Medicine report because I found it to be superior for information display as well as written in a way that the layman can either understand directly or with some supporting research. It is expensive to get this kind of testing done; however, it is far less expensive than other medical procedures. And in some jurisdictions, your health insurance may cover part or all of the cost of the testing. And in some areas, the government, Cancer agencies, hospitals, laboratories, or pharmaceutical companies may sponsor certain testing. Also, ask the companies if they offer any discounts. For example, if you inform them that you do not have medical insurance coverage.

Let the company you choose know that Ted from Glioblastoma Guide sent you. I tried to have a discount for the genetic testing provided for my viewers, but Foundation Medicine and MSK-Impact were unable to provide one at the time of recording. Perhaps with time they be able to offer something.

How many genes do they test for and why is that important?

At the time of filming this episode Foundation Medicine test named Foundation One CDx tests for 324 specific genes. And as more understanding develops in genetics and the role of different genetic errors increases the number of genes tested will likely increase for targeted analysis. The genes tested include the three main types of base substitutions, deletions, and insertions. But, can also include fusions. Over time current research has targeted the focused genes that impact cancer and are Oncogenetic drivers. As more is learned in the research and scientific communities, this information is analyzed to create a hypothesis, leading to testing, followed by clinical trials, and ultimately to targeted therapies and precision medicine. Having the largest amount of genes tested that aligns with current cancer knowledge provides more potential possibilities for a Precision Medicine to be available for your cancer.

What is the role of Precision Medicine in rare cancers?

Rare cancers have an obvious negative downside. Because so few people have these Cancers there is little research conducted to unravel the mystery of the disease. In the United States, there are approximately 10,500 people diagnosed with Glioblastoma Multiforme each year (3 in 100,000 people). By comparison, 284,000 people a year in the USA are diagnosed with Breast Cancer. 248,000 people are diagnosed with prostate cancer each year in the USA. Approximately 237,000 people are diagnosed with lung cancer each year in the USA and 186,000 people are diagnosed with leukemia, lymphoma, or myeloma. As we can see GBM is only a fraction of the cases of cancer each year. GBM accounts for less than 4% of the cases of breast cancer and if we take a total of breast, prostate, lung, and blood-borne cancers GBM is less than one percent of the total. As a result, little research funds are allocated to this terrible disease. It is so deadly, so aggressive and the Standard of Care offers very little hope. Because of this truth, we must be equally aggressive in our battle against GBM. In this case, we have the tool of Precision Medicine. If we get our GBM cancer tested genetically and receive the report it may let us know that there is no information to help; however, it could offer a targeted therapy such as a new medication. It could offer a clinical trial for the specific GBM cancer you

MSK-IMPACT analyzes 505 genes. These genes were nominated by researchers and experts from across MSK. The genes were chosen because they play a
critical role in the development and behavior of tumors. All actionable targets (genes that provide important information about the disease and possibly can be targeted with drugs) are included. MSK-IMPACT will be updated regularly as new targets are discovered. have. If you are fortunate you may discover as I did that you have the specific Oncogenetic driver for a new or existing medication that could target your GBM cancer. We do not have many tools available, and your medical team cannot keep track of every breakthrough, medication, or clinical trial available. Precision Medicine may offer this possibility. If you do have a precision medicine target you would want to know as soon as possible and to begin the process of starting treatment with this precision medicine. As I have said before, be your own best advocate and take advantage of any realistic possibilities with efficacy.

The reports I have received from Foundation Medicine have been detailed and were approximately 30 pages in length. The possibility that the NTRK Fusion marker would be found in my tumor was 1%. But that is so much better than 0%. And in my case, the marker was there, and I became the first person in Canada to be approved for the drug Larotrectinib / Vitrakvi. I will explain more about this incredible precision medicine in a future episode. Please watch for it. Who knows what or when will be the next breakthrough? There is other leading- edge research that is currently being done on many aspects of cancer treatment and specifically with Glioblastoma. Please watch my future episode on Glioblastoma Future Treatments. So, as much as rare cancers reduce the possibility of treatments being developed, they do have a possible Achilles Heel. If we can complete genetic testing and find results that offer precision medicine treatments we can target our specific cancer – not all cells in general such as chemotherapy where both healthy cells and cancer cells are targeted. It is similar to using a hose with a mist sprayer or using a solid stream. We direct the water to exactly where we want it to go in the garden without spraying everything to water the one plant we wish to water.

What happens in the process?

You speak to your Oncologist and medical team. A requisition request is made. Your medical team prepares the forms necessary. You request that they arrange for your tumor to be prepared by the Pathology Department for genetic testing. As an example, Foundation Medicine has specifications for the Pathology Department. The samples are prepared and then packaged and sent to Foundation Medicine. You make the payment to Foundation Medicine.

Foundation Medicine receives the sample. Once received they begin the intake and testing process. At the time of filming this takes approximately two weeks; but, as technology and testing change over time this period of time may increase or decrease. You can ask Foundation Medicine. The process takes longer at MSK-IMPACT, approximately 4-6 weeks, and can involve also sending finger or toenails as MSK-IMPACT cross test against your healthy DNA to determine what genetic differences are present in your normal cells and which are present in your cancer cells and if there are any crossovers.

Make sure to request that members of your medical team receive the report and also ensure to include yourself. Finally, you and your medical team review the report. As I have said earlier there may be no actionable information or treatments available at this time, but the

Oncogenetic drivers in your tumor will have been noted and if there are future breakthroughs in these areas you can keep up your research to note any possibilities. Or you may find there is an existing precision medical treatment or a clinical trial. You can discuss this information with your medical team, family, and friends and make your decisions going forward. Additionally, if you have a recurrence, and you have genetic testing completed again you and your medical team can compare the reports and determine if anything has changed and what may be occurring in the tumor environment.

Receiving the report

Review the report with your Oncologist, medical team and also review the report yourself. Keep the report for future reference and review as mentioned earlier. The reports I have received are 30 pages in length. There is a lot of information. Remember to review the report with your medical team. Preferably, you should review the report, write down any questions you have, and conduct some preliminary research to better understand any of the terms and allow you to ask more refined questions so you have the best information to work on with your medical team.

What are the Oncogenetic drivers of your tumor?

Oncogenetic drivers mean – Onco (Cancer) genetic (DNA driven) meaning that the cause of the cancer is a cancer-causing genetic issue such as a fusion, deletion, or overexpression. Oncogenetic drivers are the genetic cause of some cancers. These can be NTRK 1, 2, or 3 gene fusions, EGFR over expressions, and others. All of these genetic issues can cause the cell to reproduce uncontrollably. The purpose of precision medicine is to attempt to find the on or off switch for these specific genetic errors. It is much more complex than finding an on or off switch. In many cancers, there can be multiple Oncogenetic drivers, or there can be one dominant driver and a secondary or tertiary driver. Some drivers may have treatments available and some may not have treatments available. The important step is to perform the testing and discover if you have an actionable precision medical treatment or clinical trial that may be of benefit. If there is something you can do then you, your medical team, family, and friends can determine the best path forward. And remember, if there is no precision medical treatment available at this time do not lose hope. Time is our enemy with GBM. New treatments may become available and it is our job to see what reasonable possibilities with efficacy we can pursue to gain more time so that new treatment possibilities have a chance to develop. I continue to conduct a lot of research about GBM as well as looking into some of the specific oncogenetic drivers that have been identified on the genetic tests that have been completed on my GBM. As an example, you may have discovered that you have an NTRK 1 oncogenetic driver in your tumor and you get it treated with one targeted therapy medicine. In the future, this drug stops working, and you discover that another Oncogenetic driver that was identified in a previous genetic test is now the dominant Oncogenetic driver in your current tumor. This may provide your medical team with improved insight into possibilities for your treatment. Specific genetic information is valuable and may unlock doors today, or in the future for your treatment. If you are able to pursue genetic testing then I recommend it. For me, it has been a lifesaver. You can watch my episode in the future on Larotrectinib / Vitrakvi to learn more. We have a terrible adversary in GBM and having as many possibilities available to us to not only better understand our specific GBM; but, also, to potentially discover all possible viable treatments is key to our survival. I pray you will find beneficial outcomes with actionable treatments if you pursue genetic testing; but, if you do not, you can rest assured that you tried one of the best possible treatment paths in your pursuit to battle GBM. Who knows if the findings from your genetic testing could help you down the road as more treatments become available; or, perhaps some future study of the accumulated testing results could lead to a benefit for individuals diagnosed with this horrible disease in the future.
Search for possibilities in these areas.

Depending upon the specifics of your situation you will either be looking at an emergency situation where you take what is available as soon as possible or, you may have more time available to you and are taking a methodical approach to follow possible treatments. You may be in an emergency situation where your tumor is possibly inoperable and only a biopsy can be achieved, or where your GBM is not responding to standard-of-care treatment, or, you have a recurrence of GBM growing quickly. If this is the case then the incredibly quick approximately two-week timeline to receive the results will be greatly appreciated. You will know if there are any precision medicine treatments available, or, if there are any Clinical Trials that may be possibilities for you. If you have more time, you will be able to do more research and keep an eye out for any developments in any of the Oncogenetic drivers identified in your GBM. Perhaps this pays dividends immediately, or, there is always the possibility of tomorrow for a breakthrough. Keep your eyes peeled and work with your medical team, family, and friends to pursue possibilities.

If any Clinical Trials are available you can look into these at www.clinicaltrials.gov This is a great tool that allows you to read more about the trial, what they hope to achieve, what stage the Clinical Trial is at currently. For example, the following are a basic layman’s description of the various phases of drug development in Clinical Trials and are not medical descriptions or to be considered an exhaustive list or complete descriptions.

Please refer to the Clinical Trials regulators in your Country.

  • Phase 0 where testing is NOT done on humans.
  • Phase 1 – Directly after lab testing we have the initial small sample size testing done on humans to help determine if the drug works, dosing, and efficacy. For safety reasons, the sample size is very small at this phase.
  • Phase 2 and 3, Larger scale testing on humans to further refine dose, efficacy, side effects, and durability of the drug.
  • Phase 4 – Drug safety profile, further refining of information from earlier phases, and testing of any long-term side effects.
  • Phase 5 – Drug Approval.
  • Phases 1 – 4 are typically where it may be a possibility to participate in a Clinical Trial. Remember, there are risks involved and possibly direct and indirect costs as well in some trials. The Clinical Trial may be of benefit to you or it may not and there is always the possibility that the Clinical Trial may cause harm. If you have few or no options and have a terminal disease you may decide with your Medical Team, family, and friends that you wish to participate and have a chance at the benefit, or to know that your participation may help future patients with GBM or other cancers if you are involved in a basket Clinical Trial. Some Clinical Trials may test one drug or one therapy, while others may be a combination of drugs and or therapies to see if there is a synergistic benefit when combining these treatments.

Why should I do Genetic Testing of my Tumor?

Studies show that Glioblastomas are very heterogeneous in nature. They present with cellular and molecular diversity not only among tumors but also  within the same tumor. Coexistence of cells with different properties has been proven by numerous genetic studies, which suggests that glioblastomas may arise from different cell types. Various genetic changes including mutations, chromosomal aberrations, and copy number variations in both oncogenes and tumor suppressor genes have been found. Such genetic diversity implies glioblastoma is not a single
condition, but most likely a set of diseases.

Standard of care consists of maximal surgical resection followed by radiation and temozolomide chemotherapy. However, even with such an aggressive treatment in 75% to 90% of the glioblastoma cases, the tumor recurs within 7 to 10 months after surgery. Only 9% of glioblastoma patients are still alive two years post-diagnosis and these are considered long-term survivors. Major issues in glioblastoma management are its intracranial location, fast growth, and infiltrative nature that leads to incomplete surgical resection and the development of therapy resistance. Furthermore, chemotherapy offers limited options due to poor drug penetration through the blood-brain barrier. Identifying the cell of origin of glioblastoma is of great importance for patient care. If treatment could be tailored to target a specific subset of cells in every patient, the effectiveness of clinical care would be greatly improved. Besides, targeting specific cell types would lead to the design of novel drugs with minimal toxicity to other non-malignant cells
GBM is a terrible disease and we need to move to understand along and provide ourselves with the greatest possibilities of resisting this disease. Genetic testing provides us with the possibility of detecting a targeted therapy against our specific GBM; but, it also may provide the data needed to help others diagnosed in the future. In my case, genetic testing provided such a possibility and it may be for you as well.

There are always two sides to every argument. Some may ask, what are the downsides of genetic testing? This is true; but, some of the potential negatives are, anxiety while awaiting the results, inconclusive results, cost, and results that do not provide any actionable targets. All of this is assuming your treatment entails having debulking surgery where a sample of your tumor will be retrieved. So, in my opinion, the largest risk which is the surgery and having GBM in the first place has already occurred. We must realize that we may receive no benefit from the testing; however, this too is information. We can know that we tried genetic testing and unfortunately it did not reveal anything – but at least we tried. Also, anxiety while waiting is real; but, with or without the testing there is going to be uncertainty and anxiety with GBM so that argument is not as substantive. Cost is a real issue; however, your insurance may cover the costs, and compared with other medical procedures it remains reasonable, and over time Genetic Testing will become more and more affordable. I believe in the, not-too-distant future Genetic Testing will become part of the Standard of Care as it will reveal treatment options that help people in a more direct and targeted way than current methods of treatment can offer. Evaluating all of these cons brought me to the conclusion that genetic testing was right for me. Be your own best advocate and review your thoughts on the matter. Then, talk with your family, friends, and medical team to determine if it is right for you.

Remember, there are other steps you may be able to take. Each of these steps is time-sensitive and they have been important to me.
Glioblastoma is incredibly challenging; but, with some knowledge, understanding, and self- advocacy we may increase our odds of fighting this terrible disease.

I encourage you to watch the other episodes in this series and become knowledgeable so you can make informed decisions with your medical team, family, and friends.

To help make these videos possible please subscribe to my channel, watch each video to the end, click on the like button in each video, and ask your family and friends to do the same as this is fortunately not a large community of people with GBM. Additionally, any products that I suggest or recommend are linked below to which I may receive some proceeds at no additional cost to you to help with the costs of these videos. Please leave any positive or encouraging comments below and remember this is information I have learned, and it is helping me; it may or may not provide benefit to you. God bless you, I hope you find these videos helpful and can make a difference in your life. Please consult your medical team before following any steps I have taken on my journey. I will see you in the next episode.