12/06/2023
DNA Sequencing Leads To Longer, Better Lives for Cancer Patients...
Unlike many Oncologists, the tears by Dr. Thomas Roberts often saw in his office were those of Joy.
His patients had been told they had less than six months to live. But Roberts, then a fellow specializing in lung cancer care at the Dana-Farber Cancer Institute, was able to give many an extra lease on life. Because they had certain genetic mutations in their tumors, he could promise them at least another year and often three, five or more.
That, he says, is the power of genetic sequencing.
Over the last decade, matching tumor and patient genetic mutations with treatments has taken off. Guidelines now call for everyone diagnosed with advanced lung and colon cancer to get their tumor genetically sequenced, and increasingly, patients with earlier stage disease, as well.
Everyone should get their own genomes sequenced, guidelines say, if they have pancreatic or ovarian cancer, prostate cancer that’s spread, are under 50 with colon cancer or have a cancer in childhood. The sequencing looks for genetic mutations that can direct treatment and put them ‒ and some family members ‒ on alert for future tumors.
“You’re talking about people living longer and living better if they get access to the testing and the treatment,” said Roberts, now a head and neck cancer specialist at the Mass General Cancer Center.
Although not every cancer patient will benefit from sequencing, it’s a good idea for each patient to ask about it, Roberts said, so their doctor can consider whether it might benefit them.
But despite the guidelines and the common use of these approaches at major medical centers, many American cancer patients aren’t getting screened and are missing out, he and others said.
Less than half of patients who qualify end up getting their tumors sequenced, according to a 2021 study.
A study published Monday and presented this weekend at the American Society of Clinical Oncology annual meeting in Chicago shows that just 7% of patients who meet criteria to have their own genes sequenced actually do.
Sequencing would help determine if they should receive a drug shown to prolong disease-free survival in those with certain genetic mutations. “If you never get tested and you never got that drug, you missed that opportunity,” said Dr. Allison Kurian, a professor at Stanford University and an oncologist at the Stanford Cancer Institute, who helped lead the research.
President Biden has launched a “cancer moonshot” aiming to develop new tools to dramatically reduce cancer deaths.
“It’s one thing to invent a very cool new (treatment),” Kurian said. “But if you can’t get it out there, it really doesn’t matter.”
Why sequence a tumor
In some cases, therapies are available based on genetic mutations in the tumor itself.
Cancer starts with normal cells that transform through random mutations into rapidly reproducing cancerous cells.
Chemotherapy is directed at these quickly dividing cells, but isn’t specific to the tumor, so it also kills normal cells in places like the gut and skin, causing side effects.
Drugs that target cells with certain mutations can effectively kill cancer cells while mostly leaving healthy cells alone, Roberts said.
About 200,000 Americans will be diagnosed with non-small cell lung cancer this year and about one-third of them will have mutations on their EGFR gene.
In a study presented Sunday at the cancer conference, the AstraZeneca drug Tagrisso, which targets EGFR, cut 5-year cancer deaths in half when given after surgery.
And the more tumors are sequenced, the more researchers realize some cancers originating in other organs, such as the kidney, might have the same mutations as those originating in the lungs and so might benefit from the same targeted treatment.
In other cases, people can avoid certain treatments ‒ and their side effects ‒ because tumor genetics suggest the drug wouldn’t work. A breast cancer patient whose tumor has a certain mutation in the estrogen receptor gene, for instance, wouldn’t benefit from a class of drugs called aromatase inhibitors.
But first, those mutations have to be detected with genetic sequencing of a tumor, Roberts said.
“Knowing what is best for patients is only a small part of what actually determines whether or not they get the care,” he said.
Why not everyone gets their tumor sequenced
Medicaid will pay for treatments based on tumor genetics, but in some states, it won’t cover the genetic screening needed to determine whether a patient should get the drug, Roberts said with frustration. He thinks policies need to be changed to ensure that anyone who could benefit from a covered medication gets necessary testing.
Prior authorization requirements also can be a stumbling blocks, he said, as can the $3,000 to $4,000 cost of testing. The price of genomic sequencing itself has dropped substantially, but the cost of analyzing those results remains high, he said.
Some patients may be hesitant to get tested, said Dr. Stephen Gruber, chair of the Center For Precision Medicine at City of Hope, a national cancer research and treatment organization.
“Some groups of people have reasonable and appropriate concerns about whether medical advances are in their best interest,” he said.
Many health care systems lack support personnel and processes to quickly deliver test results and direct care as a result of them, said Dr. Marie Suga, a thoracic medical oncologist and chair of Kaiser Permanente’s National Lung Cancer Program.
While most academic medical centers have in-house labs, other institutions have to send out tumor samples for testing, which can take three or four weeks or longer. “It’s a very anxious time,” for both patients and doctors, Suga said, and many patients are quickly put on chemotherapy rather than wait to figure out what might be a more appropriate targeted therapy.
Another barrier to genetic testing, Suga said, is the “education gap.” Academic researchers work with genetic tests all the time and are generally specialists in one type of cancer. But oncologists in the community ‒ who treat 80% of all cancer patients ‒ might see a range of tumor types, each with different guidelines, making it hard to keep track. Older clinicians trained before the era of genomics may not fully understand the potential.
Since 2018, Kaiser Permanente has routinely tested tumors in patients with advanced cancers, Suga said, and doctors have often been surprised to find mutations for which there are targeted treatments.
“If you don’t test, you just don’t know,” she said. “You may be missing out on important potential additional options for treatment.”
Why sequence the person with the tumor?
In some cases, it make sense to sequence the patient themselves in addition to or rather than the tumor.
Some patients carry genetic mutations that make them more prone to cancer.
People with mutations in the BRCA1 or BRCA2 genes, for instance, are at higher than average risk for breast, ovarian, prostate and pancreatic cancers and may want to consider surgery before potentially lethal cancers can develop.
Other families carry genetic syndromes that make them prone to a variety of cancers. Knowing that vulnerability can lead to more frequent screening and can be potentially life saving.
But the new study, published Monday in JAMA, found many patients are missing these opportunities.
The study looked at nearly everyone diagnosed with cancer from 2013-2019 in California and Georgia. For ovarian cancer, where genetic sequencing has been recommended for every patient for many years, only about 38% of patients received the screening. For pancreatic cancer, by the end of the study period, 18% of patients were getting genetic screening.
The study didn’t reveal precisely why screening is falling so short. “But it probably is the usual causes that we see in so many settings: It’s structural racism, access issues, issues in terms of care quality and lots of other things,” Kurian said.
Genetic knowledge is particularly important for people with advanced cancers, Kurian said. “It’s recognized as standard of care when you have a patient with metastatic disease.”
It’s also important to sequence the genetics of children with cancer, said Paul Boutros, a cancer data scientist at the David Geffen School of Medicine at UCLA. On the order of 30% to 60% of children with cancer will benefit from getting their genes sequenced, both to match the child to the right course of therapy and to reduce treatment toxicity. Children who receive the chemo drug cisplatin, for instance, are at high risk for hearing loss if they have certain mutations, he said.
Sequencing a person can be particularly challenging because it has implications for others, said University of Michigan’s Dr. Steven Katz, an expert in treatment decisions made between patients newly diagnosed with cancer and their clinicians.
If a patient has a BRCA1 mutation, for instance, at least one of their parents likely carries it, and any children, aunts, uncles and cousins are at risk, too.
Patients are stuck in the impossible situation of deciding whether and how to tell family members about the results ‒ typically without any support from the medical system, said Katz, who co-authored the new study with Kurian. “The doctors, the clinicians, the genetic counselors are completely failing to help families,” he said. “They know it, but they don’t have the bandwidth and they aren’t incentivized for it and they aren’t insured for it.”
New Blood Test Capable Of Detecting 50 Different Types Of Cancer
New Blood Test Capable Of Detecting 50 Different Types Of Cancer
Sequencing and its benefits are not equally spread
A study Roberts co-authored earlier this year confirms that where someone lives makes a big difference in whether they or their tumor get sequenced.
In Arkansas, only 18% of Medicaid-funded lung cancer patients with ALK- or EGFR mutations received treatment targeted to their tumors, the study found, while 113% of patients in Massachusetts did (possibly because people go outside their home state to get their care).
Boutros said he expects people in urban areas are more likely to get testing, along with people who are white and those of higher socioeconomic status. Testing might also vary by age, he said, because of differences in insurance coverage, with older people, children and young adults more likely to have coverage than those in between.
This uneven use “really impinges on our understanding of where genetic testing should be best done,” Boutros said. “It’s both a moral and a biomedical imperative to do a better job at making sure that it’s offered widely.”
So far, most of the cancer-associated mutations have been identified in people of European or Chinese ancestry, so those with a different heritage might not benefit as much, he said.
As the science continues to improve, patients will have more opportunities to be matched with safe and effective treatments, said Dr. Matthew Meyerson, a cancer geneticst at Dana-Farber.
“The amount of data that exists is still growing,” he said. “It’s not going to be complete for a long time.”
Eventually, it will make sense to genetically sequence every cancer patient as well as their tumor, said Dr. William Catalona an expert in the genetics of prostate cancer at Northwestern University.
With just one or the other, “you only have half the picture,” he said
