Mutations in the BRAF gene have recently become the subject of significant attention. At this point, it is clear that having a BRAF mutation means that a colon cancer has a worse prognosis. However, there is no current suggestion that these patients should be treated differently and the anti-EGFR antibodies (cetuximab and panitumumab) can still be considered. Even though these drugs do not seem to work in patients with a KRAS mutation, most studies suggest that they can still work in patients with BRAF mutations but perhaps not as well. Unfortunately, the specific drug that blocks BRAF that is successful in melanoma (a cancer that has 50% BRAF mutations) did not demonstrate much activity in BRAF mutant colon cancer.

Most people believe that the sequence does not matter as much as making sure that all patients eligible to receive all active agents do so at some point. While in the US, the regimen of FOLFOX is often given first, there is no evidence to suggest one cannot give other regimens ie FOLFIRI first instead. In the clinical trials that have looked at these issues, it seems clear that there is little difference in receiving one regimen first and one second. It all depends on which side effects are less desirable and what is right for an individual patient.

There are some hereditary conditions that can predispose a person to developing gastric cancer. Some cases of Lynch syndrome (which more commonly causes colon cancer) can also cause gastric cancer. A rarer disorder is an inherited mutation in a gene called E-Cadherin which can lead to Hereditary Diffuse Gastric Cancer, this is extremely rare and is usually seen in families who have multiple members who have gastric cancer. If one has a strong family history of this disease, it should be discussed with the oncologist and one could consider genetics counselling.

There are many factors on the pathology report that determine if a person should receive chemo after early stage (stage 2) colon cancer. We identify any high-risk features that may be present which include a perforation, obstruction, T4 stage (meaning the tumor involves other organs near the colon) or if there was less than 12 lymph nodes sampled. There are also some features that are very low risk ie microsatellite instability (MSI) and they often do not get therapy. In the end, this is a decision that needs to be made between the patients and treating physician as it is a personal choice which has no right or wrong answer. It is a complicated topic that requires a careful and thoughtful discussion about the pros and cons of each option.

Most people believe that in any patient with advanced gastric cancer, they should receive two classes of chemo (Platinums and Fluoropyrimidines). The platinum options are cisplatin or oxaliplatin while the fluoropyrimidines include 5-FU or the oral drug capecitabine. Some people also include the taxane drugs docetaxel as well although many use them in later lines of therapy. The stage of the cancer does matter because the treatments are different if it's stage 3 vs stage 4. In patients with stage 4 disease, they are typically treated with chemo alone while most patients with stage 3 gastric cancer that has been fully removed, often receive chemotherapy and radiation together.

Currently, the only approved targeted therapy approved for gastric cancer is trastuzumab (herceptin) whose target is the HER2 protein. HER2 is overexpressed in about 20-25% of patients with gastric cancer and it should be tested in all patients diagnosed with metastatic gastric cancer. A large clinical trial called the ToGA trial determined that adding herceptin to chemo in patients with HER2 positive gastric cancer was beneficial. This is a true example of targeting a specific patient population. Dozens of other targeted therapies are currently being tested in gastric cancer all over the world but so far other than herceptin, none have been approved for clinical use.

In the Unites States, many patients that are diagnosed with gastric cancer will see the oncologist only after they have undergone surgery to remove the cancer. Once the diagnosis is established by a gastroenterologist, patients are often referred directly to surgery. However, over the last decade we have seen more patients referred to medical oncologists before surgery. This is because for many patients with gastric cancer, it is now considered preferable to undergo neoadjuvant chemotherapy (before surgery). Because gastric cancer is still quite rare in this country (25,000 cases annually), we still believe that the best approach is a multi-disciplinary one and involving an oncologist first is a good approach.

Therapeutic clinical trials are designed to improve the current standard treatment of cancers. This often involves adding additional drugs to the existing standard of care agents but sometimes involves comparing two existing standard approaches to see which is better. Designing clinical trials is also done in combination with scientists to see if an observation that was seen in a lab or an animal can be confirmed to be relevant in a human. The most important priority in designing clinical trials is making sure that the trial is being done safely in a careful, and experienced environment. Most clinical trials are collaborations between multiple institutions and usually with industry partners as well. Some trials are funded by the government and some directly by the company. All clinical trial volunteers are very much appreciated as their participation is what will help us improve our treatment.