Colorectal cancer prognosis. Adaptive clinical trials. Prediction of response to treatment. 8-1

How to predict survival for each colorectal cancer patient? How precision medicine treatment of colorectal cancer can influence prognosis? How to adapt targeted colon caner chemotherapy to every patient? Leading colorectal cancer oncologist and research expert discusses colon cancer prognosis and treatment options.

Much is written about prognosis in stage 2, stage 3 and stage 4 of colorectal cancer. Dr. Anton Titov, MD. But we learn that colon cancer is not just one entity. It is perhaps a dozen or so of different diseases labelled “colorectal cancer.” Prof. Dr. Hans-Joachim Schmoll, MD. Colon cancer prognosis by stage or by TNM classification perhaps obscures differences at the molecular level of colon cancer tumors. Let’s perhaps reformulate the prognosis question. What are the important factors that influence the prognosis in a particular colon cancer patient? These factors come from colon cancer tumor. They also reflect the body of the patient. We cannot answer this question in a few sentences. Prof. Dr. Hans-Joachim Schmoll, MD. A new colon cancer classification takes into account molecular expression types of colon cancer. Dr. Anton Titov, MD. New colon cancer classification also includes the clinical stage, location of the tumor, sex of the patient. Classification of colon cancer is also important for personalized therapy selection. For chemotherapy treatment. We have to identify specific tumor mutations. For example, KRAS or BRAF mutation in colon cancer tumors affects treatment and prognosis at every stage. we have two problems in colon cancer prognosis prediction. Prof. Dr. Hans-Joachim Schmoll, MD. One is anatomical location of the tumor and gross pathological stage of tumor invasion. The other factor that affects prognosis is molecular mutations in the colon cancer tumor itself. With time we will come to more detailed understanding of many stages and types of colon cancer tumors. We will know how exactly to treat each patient. But at the moment we are relatively limited by the data coming from prospective clinical trials. Dr. Anton Titov, MD. However, we know several important factors in colon cancer prognosis. There was a clinical trial that I organized in Germany. It was done in collaboration with Roche. Prof. Dr. Hans-Joachim Schmoll, MD. I can say about the company without conflict of interest because similar international trials were done in the UK. Also clinical trials in Toronto, Canada and other countries have led to similar conclusions about prognostic factors in colorectal cancer. the aim of this clinical trial was to find new targeted colon cancer chemotherapy medications. The goal was to identify new early, first line colon cancer therapy. Not at advanced 4th and 5th line chemotherapy of colorectal cancer. But at the beginning of the treatment. Searching for new 1st line of treatment options is difficult. Prof. Dr. Hans-Joachim Schmoll, MD. Because we already have effective chemotherapy for newly diagnosed colon cancer patients. what we do is this. We give three months of standard chemotherapy. It is effective for majority of these patients, at least from the beginning. Then we have the phase this we call the maintenance phase. We aim to maintain the effect of the first induction chemotherapy. We give 5-fluorouracil and Bevacizumab as maintenance chemotherapy. Dr. Anton Titov, MD. Colon cancer patients can be treated with this combination for a long time. we compare this standard maintenance chemotherapy with combination of different experimental colon cancer medications. Prof. Dr. Hans-Joachim Schmoll, MD. We use different experimental colon cancer medication combinations. Sometimes one arm of clinical trial is finished, we do not stop clinical trial. We next try a different chemotherapy combination. This is called adaptive clinical trial design. This is a more modern design of clinical trials. It has bayesian analysis of chemotherapy in on colon cancer. This enables us to have one big clinical trial. We put all chemotherapy combinations into the same patients. We test medications at the same time and under the same diseases. We have good information about the value of these different colon cancer medications. Dr. Anton Titov, MD. This is the first major adaptive clinical trial for patients who start induction colon cancer chemotherapy.