In clinical practice, oncology treatment always encounters a lot of clinical questions. Recently, Professor Axel Grothey gave answers to the most frequently asked questions by oncologists in the field of colorectal cancer. He is a professor of medical oncology at Mayo Clinic, Minnesota, USA, vice chairman of North Central Cancer Treatment Group (NCCTG) and co-chairman of NCCTG GI Committee. member of PracticeUpdate Oncology Advisory Committee. 1. Question: Do we need to test for all RAS mutations? Answer: The answer is yes. The question now is who will provide these tests? Commercial providers who are currently capturing the market have made this clinical practice possible. 2. Question: If mutation testing is not performed, are there side effects in patients with RAS mutations who receive treatment? Answer: There is a possibility that they may occur. Studies from Jean-Yves Douillard’s study PRIM and the current FIRE study, which added panitumumab to oxaliplatin-based and cetuximab to irinotecan-based therapy, respectively, both suggest that patients with RAS mutations can experience side effects. Not statistically significant differences were observed for all side effects, as the sample sizes of these studies were small, but the trends in their results were not encouraging. Given our current level of knowledge, I would be hesitant to add cetuximab and panitumumab to chemotherapy if all RAS test results were not available. This is an important point. 3. Question: Can I apply panitumumab after cetuximab treatment? Can panitumumab be effective when a patient’s disease progresses after cetuximab treatment? Answer: The consensus opinion is negative and panitumumab treatment will be ineffective. If the patient is allergic to cetuximab, it can be replaced with panitumumab after cetuximab therapy is stopped. Panitumumab is a fully humanized antibody, whereas cetuximab is a chimeric antibody (mouse/human), and it is clear that patients are at higher risk of cetuximab allergy, so they can be replaced with panitumumab after cetuximab allergy, but the efficacy will not be increased again. 4. Question: What is the appropriate dose for maintenance therapy? What is the optimal maintenance therapy strategy? Answer: We explore induction/maintenance therapy as a first-line regimen for a variety of tumors including ovarian, lung, and colorectal cancers. In the case of colorectal cancer, for example, induction therapy is actually required before starting an oxaliplatin-based regimen. This is because patients have to stop oxaliplatin treatment before tumor growth because of the tendency to develop sensory neuropathy and toxic accumulation. Therefore the convention is that induction/maintenance therapy is needed, and this is why fluoropyrimidine in combination with bevacizumab is recognized. Evidence from different clinical trials, both earlier and more recent, confirms the effectiveness of combination therapy. This includes the CAIRO-3 study from the Dutch Colorectal Cancer Group, presented in ASCO, which showed that fluorouracil combined with bevacizumab as maintenance therapy undoubtedly prolonged disease-free survival compared to no maintenance therapy (no chemotherapy intervention at all). There was also a trend towards longer overall survival, with a difference of 3.7 months, which was not yet statistically significant at short-term follow-up, but will be statistically significant at long-term follow-up. I am convinced that low-dose capecitabine in combination with bevacizumab is a very effective maintenance regimen. Capecitabine 625 mg/m2, bid, was applied for 2 weeks of treatment with 1 week off and bevacizumab added every three weeks. This maintenance regimen is simple and easy to implement. 5. Question: Can surgery be an option for critically resectable liver metastases? Answer: The answer is always no. Resectability is only a bystander judgment. We need a good multidisciplinary team to make this possible, and the multidisciplinary team should have a good radiologist who can locate the exact spot where we find the lesion.