美国国家公共电台 NPR For Now, Sequencing Cancer Tumors Holds More Promise Than Proof

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DAVID GREENE, HOST:

Cancer patients are increasingly having the DNA¹ of their tumors analyzed³ in a quest for better treatment. This is a prime example of what's known as precision medicine. That's where medical decisions are driven by data. NPR health correspondent Richard Harris reports that while there are high hopes about precision cancer treatment, the results often don't live up to the expectations.

RICHARD HARRIS, BYLINE⁴: When you hear stories about the use of DNA sequencing as part of cancer treatment, chances are they are uplifting stories, like that of Ben Stern who showed up one day in October for a follow-up appointment at the Johns Hopkins Kimmel Cancer Center in Baltimore.

BREE BYRD: We're going to the dark-blue chair. Of course, you know that.

HARRIS: Medical technician Bree Byrd settles him in gently.

BYRD: So they want to get a whole bunch more blood from you, so I have to take two today.

HARRIS: In the spring of 2016, Ben Stern was diagnosed with a deadly brain cancer, glioblastoma. He was 45 at the time. Surgeons removed what they could of the tumor². Then over the months, he got chemotherapy and radiation. He even got on a clinical trial to see if a leading edge drug called a checkpoint inhibitor would work. But he says that didn't prevent a tumor-induced seizure⁵.

BEN STERN: My whole right side clenched⁶ up, and Tara had called my 911 in the middle of it.

HARRIS: His wife Tara says another brain surgery led to yet more disappointment at a monthly follow-up appointment.

TARA STERN: The tumor had already grown back, and it was already bigger than the original sized tumor that we found the previous May. So it - you know, he took this little nugget out in March, and it grew back to this full-scale tumor that was causing more damage.

HARRIS: It did that in a month?

T. STERN: It did that in five weeks, yes.

HARRIS: Stern's doctor sent a genetic⁸ analysis of the cancer to what Hopkins calls its molecular⁹ tumor board. It's a small group of doctors who meet Mondays to review these genetic tests. They found an overactive gene⁷ that sometimes responds to a particular drug. So Ben went on it.

T. STERN: He started his next round of chemotherapy that Monday. But he didn't seem to get weaker. Like he was getting stronger kind of almost every day. It was - (laughter) it was almost miraculous¹⁰.

HARRIS: Ben says the drug even reversed his deteriorating¹¹ mental state brought on by the brain tumor. At the next monthly appointment, following a brain scan, Ben and Tara got more good news.

T. STERN: The tumor was immeasurable on that next MRI.

HARRIS: What do you mean?

T. STERN: It wasn't there, (laughter) to put it bluntly.

B. STERN: I was basically, as I am now, just in tears.

HARRIS: That gave Ben and Tara a sense that maybe they could conquer this cancer. His doctor at Hopkins, Matthias Holdhoff, was guardedly optimistic when we spoke¹² in October.

MATTHIAS HOLDOFF: We have to use these results with caution because we do not know how long this effect might wear on. But for the time being, this is a clinically very meaningful benefit.

HARRIS: It seemed like a success story in the making for precision medicine. But most stories like this don't have happy endings.

BEN PARK: We're getting better. But like many things in life, there's kind of hope and hype. And I think that that's also the reality with precision medicine right now.

HARRIS: Ben Park is an oncology professor at the Sidney Kimmel Comprehensive Cancer Center. After noticing how much confusing genetic information was flooding into doctors at Hopkins, he founded the molecular tumor board.

PARK: The reason I started this tumor board many years ago now - well, many being four - was simply because there was a patient - young woman who had metastatic breast cancer who had a mutation¹³ on one of these reports and decided¹⁴ to forego standard-of-care therapies, which have been proven to actually prolong life in this setting, and to get on a trial on a mutation that didn't really make sense. And she went on a trial. She almost died. She had real bad toxicity¹⁵ from the experimental drug.

HARRIS: She was drawn¹⁶, Park says, by the allure¹⁷ of precision medicine. The reality though is that most of the time the tests don't offer any suggestions for treatment. Only about a quarter of patients at Hopkins are steered¹⁸ toward particular drugs or toward ongoing¹⁹ clinical trials. And even that placement rate is far better than experience elsewhere. So far there's only been one randomized study to test this drug-targeting strategy. And it found no overall benefit for patients.

PARK: If you have this knowledge, it's not enough. You have to prove that acting²⁰ on that knowledge - some medical intervention²¹ will actually afford benefit for patients. That's the trickiest²², toughest part about looking at all these types of genomic tests to really prove that this is making a difference in the lives of our patients.

HARRIS: Park has since passed on leadership of the molecular tumor board to his colleague, oncologist Josh Lauring. Dr. Lauring says there are a few cancers where DNA analysis does make a clear difference - say in melanoma and certain types of lung cancer.

JOSH LAURING: In other cancers, it's really kind of an open question. At the same time, this testing is available commercially, as well as in academic medical centers, and is being done. Patients want it. Providers want it.

HARRIS: So what's happening, in effect, is a huge poorly constrained²³ experiment involving real patients treated differently in all sorts of settings. Lauring and colleagues at Hopkins are trying to keep track of all their patients - what they got, how long the treatment was successful and how long the patients lived.

LAURING: We think it's really important to capture that information as well to try to learn from it, because in many cases it's not going to be effective. But in some it is, and it's important for us to figure that out.

HARRIS: Therapies that target specific genetic patterns are appealing because medical scientists have some sense of the biology underlying²⁴ their drugs. They aren't just killing²⁵ fast growing cells as conventional chemotherapy does.

LAURING: Unfortunately in many cases, these responses - if they occur - are relatively²⁶ brief.

HARRIS: That unfortunately turned out to be the case for Ben Stern as well. Five months after his remarkable²⁷ response, Ben started feeling weaker again. An MRI suggested the cancer might be on the move, so he went back to the hospital for another round of chemotherapy and radiation. They're hoping for the best. Richard Harris, NPR News.

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