How to select patients for surgical resection of liver metastases? Stage 4 colorectal cancer. 2

How to select patients for surgical resection of liver metastases? Stage 4 colorectal cancer. 2

How to select patients for surgical resection of liver metastases? Stage 4 colorectal cancer. 2

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How to select patients for metastatic liver cancer resection? “What really matters is biology of metastatic stage 4 colon cancer tumor.” “We are moving into an era of precision surgery.” 10-year survival has been achieved in 30% of stage 4 metastatic colon cancer patients. What criteria predict metastatic surgery success? Metastatic stage 4 colon cancer surgery patient selection criteria. Dr. Graeme Poston, MD. Colorectal cancer liver metastases patient selection. Dr. Anton Titov, MD. Liver metastases surgery depends on molecular markers in colon cancer tumor (KRAS, BRAF, NRAS, MSI). Video interview with leading British liver cancer surgeon specializing in colorectal cancer metastases resection. Number of liver metastases and size less than 3 cm is no longer important. Genetic profile of metastatic colon cancer is most important for liver resection. Advanced stage 4 colon cancer surgery for liver metastases. Dr. Graeme Poston, MD. Medical second opinion confirms that stage 4 colorectal cancer diagnosis is correct and complete. Medical second opinion also confirms that liver metastases surgery is possible in stage 4 colon cancer. Best treatment for advanced stage 4 colon cancer with liver metastatic lesions. Dr. Anton Titov, MD. Medical second opinion helps to choose the best treatment for stage 4 colorectal cancer with liver metastases. Get medical second opinion on advanced colorectal cancer and be confident that your treatment is the best. Best colorectal cancer treatment center for liver metastases. Dr. Graeme Poston, MD. Video interview with leading expert in colorectal cancer liver metastases treatment surgery. Metastatic stage 4 colon cancer surgery patient selection criteria. Dr. Anton Titov, MD. Sometimes liver metastases develop in stage 4 colorectal cancer, today some patients can still be cured. Dr. Anton Titov, MD. But it is very important to use the correct selection criteria. How to choose patients with advanced stage 4 colon cancer for liver resection. Dr. Graeme Poston, MD. Leading liver cancer surgeon. Yes. Dr. Anton Titov, MD. It is critical for the patient with advanced stage 4 colon cancer to undergo liver resection. Surgeons resects metastatic lesions resection for a chance of cure. Dr. Anton Titov, MD. What selection criteria do you use in your surgical practice? How to choose those metastatic stage 4 colorectal cancer patients for liver lesions resection who would benefit most from surgery? Dr. Graeme Poston, MD. Leading liver cancer surgeon. Right. Selection criteria for metastatic liver cancer resection has evolved. I say, 20 years ago, selection criteria for liver metastatic lesions resection were this. The number of liver metastases had to be less than three. All liver metastases had to be on one side of the liver. The patient had to be fit for surgery. Less than 10% of all patients with stage 4 colorectal liver metastases fit that definition of suitability for surgery to remove liver metastases. Dr. Graeme Poston, MD. Now we have changed selection criteria for liver resection in stage 4 colorectal cancer. It is now what you can leave behind that matters for selection of patients for surgical operation. There has to be enough healthy liver left after the surgical operation to remove cancer. That is the most important criteria for liver tumors resection. The parameters to select metastatic colon cancer patients for surgery I have just mentioned. But those things I have just mentioned. Number, size, position of liver tumors is less important. Professor Virchow and Charite Hospital in Berlin in 1890 could have told you that. Dr. Graeme Poston, MD. Leading liver cancer surgeon. What really matters is biology of metastatic stage 4 colon cancer tumor. We are moving into an era now of precision surgery. Dr. Anton Titov, MD. Precision medicine. Personalized medicine. Now, precision surgery. Precision surgery. Dr. Graeme Poston, MD. We are now looking at the genetic tumor markers and the genetic mutations in colon cancer tumors. Tumor markers will, I believe, not just be prognostic for survival of patients with advanced stage 4 colorectal cancer. Dr. Anton Titov, MD. Tumor markers will predict who will do well after surgical operation to remove liver metastases. One extreme example is BRAF mutation. Imagine that I had Stage 4 colorectal cancer. My colon cancer tumor was BRAF mutant. I would say to you this. "Give me the €100,000 you are going to waste on my treatment, because I am going to spend it on a vacation." Dr. Graeme Poston, MD. Leading liver cancer surgeon. Because no treatment works in this colon cancer situation. If you are a BRAF mutant, you do very badly. We now know the KRAS and NRAS mutations this predict response to EGF receptor treatments. Dr. Graeme Poston, MD. They actually are prognostic for patient's response to surgery to remove liver metastases in advanced stage 4 colorectal cancer. Dr. Anton Titov, MD. The wild type KRAS. Dr. Graeme Poston, MD. The wild type KRAS. Surgery can be done both for the primary colon cancer and stage 4 colorectal cancer metastases. Then patients with wild-type KRAs (NRAS) tumors do better than the mutants. Of the patients with mutant KRAS (NRAS) colon cancer tumors, codon 12 seems to be the worst KRAS mutant prognostically. We are now looking at NRAS tumor marker in surgery. We are now looking at all the mutational colon cancer tumor markers we can measure. Dr. Graeme Poston, MD. We study their impact on patient's results after surgery to remove colon cancer metastases from the liver. We are doing that in historical samples of primary liver metastases. We know the outcome of colon cancer treatment. We plan to see how liver resection surgery correlates to the genetic profile of the colon cancer tumor. We would be able to say this, for example. This patient has a two centimeter solitary metastasis on the very edge of the liver. But all important cancer genes in this colon cancer tumor are mutant. Surgery to remove liver metastases is probably pointless for that patient. Because that patient's stage 4 metastatic colon cancer will progress at multiple sites. It will spread no matter what you do. It is just at this moment in time that we see stage 4 colon cancer metastatic lesion at one tiny site. But in one month, two months later, everything will change. Dr. Graeme Poston, MD. Metastatic colon cancer in this patient will progress to multiple lung metastases and multiple other liver metastases. We look at another metastatic colon cancer tumor. It is 10 centimeters in size. Maybe two or three tumors are in the liver. But all important cancer genes in this patient's metastatic stage 4 colon cancer tumor is wild type, wild type, wild type, wild type. This patient will do well. It does not matter how big is a metastatic tumor in the liver of such patient. This is where the next five years are going to go in metastatic stage 4 colon cancer treatment. Dr. Anton Titov, MD. This is amazing! Because the surgical selection criteria for a patient with metastatic stage 4 colon cancer depend on molecular precision medicine. Selecting a patient for liver cancer resection does not depend just on the size or location of the macroscopic cancer lesion. Dr. Graeme Poston, MD. Leading liver cancer surgeon. Yes. Size and location of tumor. It is very crude. It is a century old. Professor Virchow could tell you in 1890 the size of a tumor. The color of the tumor, the location of the tumor. How many tumors there were. Dr. Anton Titov, MD. That is an amazing progress in stage 4 metastatic colon cancer liver tumor treatment. Dr. Graeme Poston, MD. Leading liver cancer surgeon. We are making huge progress in stage 4 metastatic colon cancer surgical treatment correct now. It is going hand in hand with precision medical oncology as well. Dr. Graeme Poston, MD. The very same things are dictating targeted therapy in medical oncology. In my view they will actually direct metastatic colon cancer liver surgery. Molecular profile of tumor will direct decisions whether to do surgical resection of tumor or not. Dr. Anton Titov, MD. It is really a convergence path between precision medicine and precision surgery. Dr. Graeme Poston, MD. Leading liver cancer surgeon. Yes. The last thing we have forgotten to discuss is this. Recently we have been able to show for the first time ever in a prospective randomized trial an important fact. We showed that doing a surgical operation on the liver metastases in stage 4 advanced colon cancer confers survival benefit for the patient. We set up a clinical trial 15 years ago called the CLOC Study with EORTC. The clinical trial randomized patients with unresectable liver metastases to two groups. Group one was getting chemotherapy. Group two was getting chemotherapy plus radio-frequency ablation of metastatic colon cancer tumors in the liver. Our primary endpoint was to double three-year survival from 15 months with chemotherapy alone. Dr. Graeme Poston, MD. The goal was a survival to 30 months with chemotherapy and radio-frequency ablation. Dr. Anton Titov, MD. That was a treatment of stage 4 metastatic colon cancer tumors in the liver. Both arms, median survival was 30 months. Because we never saw 15 years ago all the other lines of therapy coming. Such as second line of colon cancer therapy, third, fourth line therapy. We never saw previously targeted colon cancer therapy with Bevacizumab (Avastin), Cetuximab (Erbitux). Dr. Graeme Poston, MD. Leading liver cancer surgeon. But 10 years out, we have just presented at ASCO meeting two months ago the 10-year survival data on the clinical trial. 30% of the patients in this prospective randomized trial of stage 4 advanced colon cancer treatment survived. They had radiofrequency ablation. These patients are alive. 5% of metastatic stage 4 colon cancer patients who had chemotherapy alone are alive. Dr. Graeme Poston, MD. Even though the sample size is small, it is only 110 patients. It is highly significant result for best advanced stage 4 colon cancer treatment options. Dr. Anton Titov, MD. But it is not just five year survival. It is 10-year survival, 30% of patients who underwent radiofrequency ablation of stage 4 metastatic colorectal cancer tumors in the liver. Dr. Graeme Poston, MD. Leading liver cancer surgeon. Yes. Dr. Anton Titov, MD. That is an amazing result. Dr. Graeme Poston, MD. Leading liver cancer surgeon. Yes. Liver metastases resection in stage 4 colon cancer patient selection criteria. 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