Cancer treatments that use a strategy called immune checkpoint blockade (ICB) have entered clinical practice in a big way, with six drugs now approved by the U.S. Food and Drug Administration (FDA) for a variety of cancers. These drugs release “brakes” on the immune system, boosting its ability to kill cancer cells. Specifically, they target the proteins PD-1 or CTLA-4, which are found on the immune system’s T cells, or the protein PD-L1 on tumor and other cells. Patients’ response rates, however, have been lower than hoped for in most cancers.
Much research and discussion has focused on analysis of particular features in tumors themselves that predict how they might respond to ICB. However, because ICB drugs act on immune system proteins, it is clear that each patient’s immune system is a major player in shaping response to treatment, and that certain tumor-independent features are at play. Here’s what we know about seven factors besides tumors themselves that may predict a patient’s response to ICB: Continue reading…
A Q&A with Rama Gullapalli, MD, PhD; a a physician-scientist in the departments of Pathology, Chemical and Biological Engineering at the University of New Mexico. His research lab focuses on the role of the environment in hepatobiliary cancers. He is also a practicing molecular pathologist with an interest in emerging molecular diagnostics, next generation sequencing and bioinformatics. Email: email@example.com
Q: A recent New York Times op-ed piece from an NYU Langone Health professor urged an aggressive approach to screening for early-stage pancreatic cancer. Despite optimism, the history of cancer screening is rife with trouble, the harms often exceeding the benefits. What do you think is the best way to proceed?
A: Imagine a scenario.
A new cancer test hits the market with some impressive characteristics: a detection sensitivity of 95% and a specificity of an equally impressive 95%. If you were asked the question, “Given a positive test result, what are your chances of actually having cancer?” and you guessed a number of 80 or 90%, you would not be alone. But you’d be wrong.
The key missing information necessary to answer this question is the disease probability among the general population. The number of new cases of cancer detected every year in the U.S. is about 462 cases per 100,000 people. This means that the probability of a new cancer being detected in a member of the U.S. population annually is roughly 0.00462%. Incorporating this information leads to only an 8.1% chance of having cancer for a test that is positive! This is what is called an inverse probability problem. Continue reading…