In this Housecalls, Dr. James Kadouch discusses a rare cancer, Gastrointestinal Stromal Tumor (GIST), in the first case. The treatment of cancer is at the forefront of “personalized medicine.” In other words, as the specific mutation or molecular basis that causes a specific tumor to form and grow becomes better defined, the treatment becomes more individualized or “personal.”
Over the last 30 years or so, we have seen the evaluation of tumors go from simple histology (observing cells with different stains under a microscope) to immunochemistry (identifying particular receptors or antigens present on tumor cells) to molecular and genetic analysis (identifying over-expression of genes and proteins or individual genetic mutations). GIST treatment with Imatinib is individualized, based on whether mutations are found in the KIT gene, and the suggested dosage is higher when a specific mutation causing drug resistance is found in exon 9.
These molecular and genetic biomarkers are assuming increasing importance in cancer treatment. On May 23, 2017, the FDA approved Keytruda (pembrolizumab) “for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).” This is the first FDA drug approval based on biomarkers rather than organ of origin (e.g. breast or lung).
Pharmacogenetics is another area of personalized medicine that is being actively studied. Based on genetic variables, individuals will metabolize some common medications at different rates. This has implications for dosing or even prescribing certain medications.
Studies have shown that, in some cases, personalized information about increased risk has enhanced the likelihood that patients would change behavior (e.g. stop smoking or take cholesterol lowering medication) at a higher rate than in groups that did not have the information. We would expect to see incremental improvements in health in some cases and dramatic improvements in other situations due to personalized medical care
In the second case, Dr. William Rooney presents a classic example of combining probabilities. You multiply the probability of an event (anaphylaxis) times the probability of death due to the event to get the overall probability of death. Luckily anaphylaxis is rare, and he describes treatments to make it rarer still.
And finally, I present an unusual EKG Puzzler.