Colorectal cancer prognosis. How to predict toxicity of cancer treatment? 4

How colorectal cancer gene profiling helps to identify patients who might experience significant toxicity from chemotherapy? Use of tumor DNA and RNA and patient’s genetic data to predict colon cancer treatment efficacy. Who will not require systemic chemotherapy after resection of primary colorectal cancer?

Colorectal cancer prognosis and treatment toxicity prediction. Dr. David J. Kerr, MD. Leading colorectal cancer expert from Oxford discusses colon cancer prognosis. Dr. Anton Titov, MD. Colorectal cancer prognosis by gene profiling. Gene expression in colon cancer for chemotherapy toxicity prediction. Precision medicine in colon cancer therapy. Tumor markers help to personalize treatment for colorectal cancer. Colorectal cancer chemotherapy toxicity is predicted by tumor markers. Stage 2 colon cancer targeted chemotherapy options should be based on genetic tumor profile. Second opinion confirms that stage 2 colorectal cancer diagnosis is correct and complete. Dr. Anton Titov, MD. Second opinion also confirms that adjuvant chemotherapy for stage 2 colon cancer is required. Best treatment for stage 2 and stage 3 colorectal cancer. Second opinion and tumor genetic profile helps to choose precision medicine and the best targeted chemotherapy treatment for stage 2 colorectal cancer. Get second opinion and genetic profile on stage 2 colorectal cancer and be confident that your precision medicine treatment is the best. Dr. David J. Kerr, MD. Best colorectal cancer treatment center for personalized medicine. Dr. Anton Titov, MD. Video interview with leading expert in metastatic colorectal cancer treatment from Oxford. Colorectal cancer diagnosis and prognosis by genetic profiling. Dr. Anton Titov, MD. You write this. “We have to treat with chemotherapy a hundred of Stage 2 colorectal cancer patients to cure 3 or 4 colon cancer patients. Up to 40% of colon cancer patients treated will suffer significant toxicity. They will face distinct social and often financial inconvenience of outpatient colorectal cancer chemotherapy for six months.” Dr. Anton Titov, MD. You developed a particular method of colorectal cancer gene profiling. It is helpful in identifying those colorectal cancer patients who would benefit from the chemotherapy the most. Dr. Anton Titov, MD. Could you please discuss this colorectal gene profiling discovery? How does it help in selection of personalized therapy of colorectal cancer? Dr. David Kerr, MD (Colon cancer oncologist, Oxford).  You said this very well. We looked at prognostic markers for colorectal cancer patients. Dr. David J. Kerr, MD. We did a large experiment in collaboration with company Genomic Health. We got colorectal tumor RNA out of paraffin embedded colon cancer tumor blocks. Why is it important? Because every pathology laboratory in the world is very good at handling tumor specimens embedded in paraffin. This gives us a large tumor sample base to work on. Extracting RNA for molecular profiling from embedded colorectal tumor sample is difficult technically. We worked on genomic profiling of colorectal cancer with Genomic Health and with NSABP . It is a large American clinical trials group. We studied 4,000 patients with colorectal cancer. We identified a set of 7 genes. These 7 genes can identify Stage 2 colorectal cancer patients, who were most at risk of relapse in cancer. Expression pattern of these 7 genes showed important information. It identified patients who will benefit from adjuvant chemotherapy to treat Stage 2 colorectal cancer after surgery. These 7 genes also identified colon cancer patients who had excellent prognosis. Their chance of cancer returning would be very small. They would not benefit from adjuvant chemotherapy after surgical colon cancer removal. Dr. David Kerr, MD (Colon cancer oncologist, Oxford). As you said genetic profiling of tumor would avoid excessive over-treating some colorectal cancer patients with potentially toxic chemotherapy. Dr. David J. Kerr, MD. Some patients would not benefit from colon cancer chemotherapy after surgical treatment. It is important to look at RNA profiles in colorectal cancer tumors. But it is also important to look at patient’s response to toxicity after treatment with colorectal cancer chemotherapy. This helps to predict side-effects of colon cancer chemotherapy. We have just completed some genome-wide association study. We identified germline genetic variants (SNPs). This will tell us which colorectal cancer patients are most likely to develop a life-threatening or serious toxicity. We call this “toxnostics”. We published Nature Reviews paper about this method. This genetic profiling method allows us in advance to identify those colorectal cancer patients who likely to get serious toxicity. We then can modulate colon cancer chemotherapy dosages. In some cases we can find colorectal cancer patients. For them the risk of death from chemotherapy toxicity is very high. These cancer patients should avoid chemotherapy altogether. Dr. Anton Titov, MD. Putting together a genetic profile of tumor and host gives us a very complete picture. We can find those patients who would benefit most from colon cancer chemotherapy. Dr. Anton Titov, MD. It’s a true personalized medicine example. You study not only the tumor, but also the patients. Precision medicine on both sides is an example of modern colon cancer treatment. Dr. David Kerr, MD (Colon cancer oncologist, Oxford). Exactly! We cannot disregard genetics of both colon cancer tumor and its “host”, the patient. The two are intimately linked together. We have to treat the whole colorectal cancer patient. We do not treat just the colon cancer tumor. We cannot treat the colon cancer independently of the patient. We have to combine the knowledge of colon cancer tumor biology with how the host (the patient) responds to chemotherapy on a genetic level. This approach allows us to look at both sides of cancer treatment. It takes precision medicine to treat colorectal cancer patients to a new level. We combine efficacy and toxicity knowledge to treat colorectal cancer patients. Dr. Anton Titov, MD. As you highlighted, no special preparation of tumor sample is required. Therefore the standard preparation of colon cancer biopsy or surgical excision of tumor can be applied to DNA microarray testing. Dr. David Kerr, MD (Colon cancer oncologist, Oxford). Molecular profiling of colon cancer tumor on paraffin embedded samples makes it so much easier. Because it is difficult to obtain fresh frozen tumor samples in large quantities. It’s a problem even in a sophisticated clinic like Oxford. Getting fresh frozen colon cancer tumor tissue from the patient into the laboratory is difficult. Even out fantastic pathology laboratory has problems with it. Dr. Anton Titov, MD. Colorectal tumor genetic profiling from paraffin embedded tumors makes it much easier. Our science then can be used by many more laboratories around the world. Dr. Anton Titov, MD. This is a very important achievement. It helps to treat patients further. It will help to reduce colon cancer treatment toxicity. It will improve efficacy of colorectal cancer treatment. Dr. David J. Kerr, MD. We will apply precision medicine (personalized medicine) to colon cancer treatment. We will identify better prognostic factors. Tumor molecular markers predict colon cancer prognosis and treatment toxicity. Tumor gene profiling helps to select best colon cancer therapy. 40% toxicity.