In the discussion session, Douglas A. Levine, MD, Head of Gynecology Research Laboratory at Memorial Sloan Kettering Cancer Center, said that while advanced genomics can help to predict outcomes, stratify treatment, and understand biology, one of the problems of precision medicine is that clinicians’ efforts are hampered by intratumoral heterogeneity across space and time.

“Whatever initiates a tumor and is present in the [primary site] may be completely different from what allows that tumor to metastasize to other parts of the body and then invade or live in those areas,” said Dr. Levine. 

Douglas A. Levine, MD

The second problem of precision medicine, he added, is dealing with the heterogeneity of the tumor across treatment. After primary treatment, a patient may go into complete remission, but that tumor, which may still be present in undetectable quantities, has now been subjected to cytotoxic therapies. 

“With each line of therapy,” said Dr. Levine, “you’re changing that population of tumor cells so that, across time, there’s also molecular heterogeneity.”

Window Into Complexity

According to Dr. Levine, circulating tumor DNA may provide a window into the complexity of intratumoral heterogeneity, leading to more accurate precision medicine. 

“To be clear,” said Dr. Levine, “we don’t just want precise medicine; we want accurate precision medicine. Every time that we give paclitaxel and carboplatin to an ovarian cancer patient, it’s incredibly precise: We’re giving the same treatment every time, but we’re not really hitting the target. Precision medicine is good, but it’s a bit of a misnomer. What we really need is accurate medicine to actually hit those targets.”

Through technology such as circulating tumor DNA, he explained, physicians can move each patient closer to the benefits of accurate precision medicine.

“Ultimately, the goal is to identify a target and then develop a treatment that will lead a patient to have a complete and sustained response for many years,” Dr. Levine concluded. “Circulating tumor DNA may help us either to understand or overcome the complexities of intratumoral heterogeneity. In most situations, the primary tumor is likely a poor surrogate for recurrent disease.” ■

Disclosure: Dr. Levine reported no potential conflicts of interest.