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All too often I find myself flying across the country. As it happens, I tend to request a window seat in airplanes; I like to look out and keep track of where I am as I fly across this great land. When one flies from Washington, DC to the West Coast, just past West Virginia and all the way to Denver, the view out the airplane window looks essentially the same. Where are we? Are we over Indiana? Are we over Oklahoma? Are we over Iowa? It is frequently difficult to tell. Often, there are major identifiable landmarks, such as rivers or towns that help us to determine exactly where we are. I think East Coasters, like me, frequently question whether or not we really care where we are, imagining that the entire middle section of the United States is one homogeneous mass of people. However, I know well that it matters a lot whether one is from Kentucky, or from Tennessee, or Oklahoma versus Iowa. These are very different places with very different people and very different cultures.
As I think about this, gazing out my window at the puzzle below, I am reminded of the job our pathologists must do as they gaze down through their microscopes looking at immunohistochemical stains of our patients’ tumors. Our pathologists will sometimes look for major landmarks or localizing traits to determine whether or not the tumor arises from the colon, the duodenum, the ampulla, or elsewhere. But whether the tumor originates in the colon, pancreas, gallbladder, or small intestine, in the end, they all turn out to be adenocarcinomas. The vast majority of cancers I treat are adenocarcinomas. The question is, are they all the same cancer? Should we be treating them all the same or should we begin to distinguish them as different cancers?
Data presented at ASCO this year and in recent journals have shown that we are trying very hard to distinguish these different types of tumors. Data presented at this year's annual meeting looked at applying an Oncotype DX-type analysis to colon cancer to distinguish risk, with the hope of also predicting therapeutic outcomes. While on one level, the Oncotype DX analysis proved useful in stratifying patients at risk—in other words, a prognostic marker—it failed to be a predictive marker of who would benefit from chemotherapy. Well, this is still a step in the right direction. We should not be treating all adenocarcinomas the same, and we should begin to learn how to distinguish them at the molecular level.
Unfortunately, we left ASCO on softer ground than we had started out on, and quite honestly, that was not due to the amount of rain that we had while we were in Orlando. We went in to the ASCO meeting thinking that microsatellite instability, epidermal growth factor receptor and KRAS mutation status were very useful and highly predictive markers. While they still may remain a standard approach, we learned from ASCO this year that the microsatellite instability story is not as pure as we once thought, and more recent data from the Journal of Clinical Oncology suggests that even KRAS mutational status does not necessarily predict for benefit rate in patients with colorectal cancer.
We should not be treating all adenocarcinomas the same, we should begin to learn how to distinguish them at the molecular level.
Obviously, FOLFOX is not the answer to all adenocarcinomas. Imagine being a breast cancer specialist—the very notion would make your skin crawl! Treatment would never stop there; you would want to know a patient’s ER, PR, Her2/Neu status, and now there’s DNA array-based gene expression to be considered — these diagnostic tools yield valuable information about which therapeutic strategies to pursue. We in GI cancer, on the other hand, have been stuck, looking out the airplane window and making all our decisions from that vantage point. So, as we continue to fly along and look down trying to discern where we are, we must continue to recognize that we are a bit lost and we need to continue to look out of the window and figure out the landmarks, so that we may offer our patients the best therapeutic options as we move forward.