Unlike many oncologists, the tears Dr. Thomas Roberts often saw in his office were tears of joy.
His patients were given less than six months to live. But Roberts, then a researcher specializing in lung cancer treatment at the Dana-Farber Cancer Institute, was able to give many more lives. Because their tumors had certain genetic mutations, he could promise at least another year, often three, five, or more.
That’s the power of gene sequencing, he says.
Over the past decade, we have begun to adapt tumor and patient genetic mutations to therapy.
Guidelines now require all people diagnosed with advanced lung or colon cancer to have their tumors sequenced, and increasingly include patients with early-stage disease as well. there is
According to the guidelines, everyone with pancreatic or ovarian cancer, metastatic prostate cancer, colon cancer under age 50, or childhood cancer should have their genome sequenced. It says. Sequencing looks for genetic alterations that may direct treatment and warn the person or some family members about future tumors.
“It means people live longer and have better lives if they can get tested and treated,” said Roberts, now a head and neck cancer specialist at the Massachusetts Comprehensive Cancer Center.
Not all cancer patients will benefit from sequencing, but it’s a good idea for each patient to ask about sequencing so doctors can consider whether it would be beneficial, Roberts said.
But despite guidelines and the common use of these approaches in major medical centers, many U.S. cancer patients are not being screened and are missing out, they said.
Fewer than half of eligible patients will eventually have their tumors sequenced, according to a 2021 study.
According to the study, which was announced Monday and presented at the American Society of Clinical Oncology Annual Meeting in Chicago this weekend,% Some of the patients who meet the criteria to have their own gene sequenced actually have that gene sequenced.
Sequencing could help determine whether drugs that have been shown to prolong disease-free survival in patients with specific gene mutations should be given. “If you never get tested and don’t get the drug, you’ve missed the opportunity,” said Allison Kurian, PhD, a Stanford University professor and oncologist at the Stanford Cancer Institute, who led the study. said.
President Biden has launched a “cancer moonshot” that aims to develop new tools to dramatically reduce cancer deaths.
“It’s another thing to invent a really cool new[treatment],” Kurian said. “But if you can’t get it out, it doesn’t really matter.”
Why Sequencing Tumors
In some cases, treatments are available that are based on genetic mutations in the tumor itself.
Cancer begins as a normal cell that undergoes random mutations to transform into a rapidly growing cancerous cell.
Chemotherapy is directed at these rapidly dividing cells, but because it is not specific to tumors, it also kills normal cells, such as those in the intestine and skin, causing side effects.
Drugs that target cells with specific mutations can effectively kill cancer cells while leaving mostly healthy cells, Roberts said.
almost 200,000 Americans will be diagnosed with non-small cell lung cancer about this year 1/3 of them will mutate About the EGFR gene.
In a study presented at Sunday’s cancer meeting, AstraZeneca’s drug Tagrisso, which targets EGFR, Administered after surgery halves cancer deaths within 5 years.
And as more tumors are sequenced, some cancers from other organs, such as the kidney, may harbor the same mutations as those from the lung, potentially benefiting from the same targeted therapies. Researchers become aware that they may be subject to
Also, certain treatments and their side effects may be avoided because tumor genetics suggest that the drug is ineffective. For example, breast cancer patients who have certain mutations in the estrogen receptor gene in their tumors cannot benefit from a class of drugs called aromatase inhibitors.
But first, these mutations need to be detected by gene sequencing of the tumor, Roberts said.
“Knowing what’s best for a patient is only one part of deciding whether or not to actually get treatment,” he says.
Why isn’t everyone getting their tumors sequenced?
Medicaid will pay for treatment based on a tumor’s genetics, but some states don’t cover the genetic tests needed to determine if a patient should be given the drug, Roberts said. complained. He believes policy needs to change to ensure that people who might benefit from reimbursed drugs get the tests they need.
He said pre-approval requirements could be a roadblock as well as the $3,000 to $4,000 cost of testing. Although the price of genome sequencing itself has come down significantly, the cost of analyzing the results remains high, he said.
Dr. Steven Gruber, director of the City of Hope Center for Precision Medicine, the national agency for cancer research and treatment, said some patients may be hesitant to get tested.
“Some people have reasonable and appropriate concerns about whether medical advances are in their best interests,” he said.
Marie Suga, M.D., thoracic medical oncologist and chairman of Kaiser Permanente’s National Lung Cancer Program, said many healthcare systems need support to provide rapid test results and direct treatment accordingly. They said they lacked people and processes.
Most university medical centers have in-house laboratories, but other facilities require tumor samples to be sent for testing, which can take 3-4 weeks or longer. “It’s a very anxious time,” said Suga, for patients and doctors alike, with many patients getting chemotherapy right away without waiting to find out what a more suitable targeted therapy is.
Another barrier to genetic testing is the “educational gap,” Suga said. Academic researchers are always working on genetic tests, and usually he’s an expert on one type of cancer. But a local oncologist who treats his 80% of all cancer patients may see different types of tumors, each with different guidelines, making it difficult to keep track. Older clinicians trained before the era of genomics may not fully appreciate its potential.
Since 2018, Kaiser Permanente has routinely screened tumors in patients with advanced cancer, and doctors are often surprised to find mutations with targeted treatments, Suga said.
“If you don’t test it, you just don’t know,” she says. “You may be missing an important potential additional treatment option.”
Why sequence people with tumors?
In some cases, it is reasonable to sequence the patient himself in addition to the tumor or not.
Some patients have genetic mutations that make them more susceptible to cancer.
For example, people with mutations in the BRCA1 or BRCA2 genes have a higher-than-average risk of breast, ovarian, prostate, or pancreatic cancer and may want to consider surgery before they develop life-threatening cancers. I can’t.
Some families have genetic syndromes that predispose them to various cancers. Knowing your vulnerabilities can help you get tested more often, potentially saving lives.
However, new research Published in JAMA magazine on Mondayfound that many patients miss these opportunities.
The study included nearly everyone diagnosed with cancer in California and Georgia between 2013 and 2019. Although gene sequencing has been recommended for all patients with ovarian cancer for many years, only about 38% of patients were screened. For pancreatic cancer, 18% of his patients had undergone genetic screening by the end of the study period.
The study doesn’t explain exactly why testing is so lacking. “But it’s probably a normal cause in many settings. It’s systemic racism, access issues, quality of care issues and many other issues,” Kurian said.
Mr. Kurian said genetic knowledge is especially important for patients with advanced cancer. “It is recognized as the standard of care for patients with metastatic disease.”
Sequencing the genes of children with cancer is also important, said Paul Boutros, a cancer data scientist at the University of California, Los Angeles David Geffen School of Medicine. Approximately 30% to 60% of children with cancer would benefit from gene sequencing to match them to appropriate treatment regimens and reduce treatment toxicity. For example, children taking the chemotherapy drug cisplatin are at increased risk of hearing loss if they have certain mutations, he said.
Dr. Steven Katz, of the University of Michigan, an expert in treatment decisions made between newly diagnosed cancer patients and their clinicians, said that sequencing one person’s base might help others. He said it could be particularly difficult because of the impact.
For example, if a patient has a BRCA1 mutation, at least one parent is likely to have a BRCA1 mutation, and children, aunts, uncles, and cousins are also at risk.
Kurian and Katz, co-authors of the new study, said patients typically lack help from the health care system, leaving them in an impossible situation of deciding whether and how to communicate their results to their families. said to have fallen. “Physicians, clinicians, and genetic counselors are completely incapable of helping families,” he said. “They know it, but they have no bandwidth, no incentives for it, and no insurance for it.”
Sequences and their benefits are not evenly spread
A study Roberts co-authored earlier this year confirmed that where people live makes a big difference in whether a person or their tumor is sequenced.
In Arkansas, only 18% of Medicaid-funded lung cancer patients with ALK or EGFR mutations received tumor-targeted therapy. found in researchIn Massachusetts, on the other hand, 113% of patients did (probably because people are traveling outside their home state to seek treatment).
Boutros said he expected people in urban areas to be more likely to be tested, as well as whites and people of higher socioeconomic status. Testing may also vary by age due to differences in insurance coverage, he said, with older people, children and young people more likely to be covered than those in between.
This uneven use “has a huge impact on our understanding of where genetic testing is best done,” Boutros said. “It’s a moral and biomedical imperative to do a better job of making it widely available.”
So far, most cancer-associated mutations have been identified in people of European and Chinese descent, so people with different genetics may not benefit as much, he said.
Dr. Matthew Myerson, a cancer geneticist at Dana-Farber, said as science continues to advance, patients will have more access to safe and effective treatments.
“The amount of data out there is still growing,” he said. “It won’t be finished for long.”
Dr. William Catalona, an expert in prostate cancer genetics at Northwestern University, said ultimately it would make sense to sequence the genes of all cancer patients and their tumors.
With only one or the other, “you only get half the picture,” he said.
Please contact Karen Weintraub (kweintraub@usatoday.com).
USA TODAY’s coverage of health and patient safety is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation, and Competition in Healthcare. The Masimo Foundation does not provide editorial opinion.
