The Link Between Health Literacy & Cancer Communication
In an era of increasingly complex advances in oncology, how can health professionals help cancer patients with low health literacy better understand their diagnoses and treatment options? In an effort to improve cancer communication strategies with patients, the National Cancer Policy Forum (NCPF) of the National Academies of Sciences, Engineering, and Medicine (NAS) convened a meeting of invited speakers in Washington, D.C. The event was held in collaboration with the NAS Roundtable on Health Literacy. A written summary report of the meeting will follow.
At the meeting, the point was repeatedly made that skills in cancer communication can be taught and learned, and it is the responsibility of health professionals to make sure all their patients (including those with low health literacy) truly comprehend the information they are being given.
“This is a really big challenge; it's a very complex area,” said meeting co-chair and NCPF member Karen Basen-Engquist, PhD, MPH, the Annie Laurie Howard Research Distinguished Professor; Director for Energy Balance in Cancer Prevention & Survivorship; and Professor of Behavioral Science at the University of Texas MD Anderson Cancer Center.
“Low health literacy leads to poor health outcomes,” said meeting co-chair and Roundtable on Health Literacy member Michael Paasche Orlow, MD, MA, MPH, Professor of Medicine at Boston University School of Medicine. “We're talking about empowering people,” added Orlow, noting that a cancer patient with low health literacy is faced with making major decisions at a time of emotional and psychological turmoil and is therefore vulnerable. The problem has been well-defined; now, Orlow believes it is time to think about what can be done.
Identifying Health Literacy
Health literacy is generally defined as the degree to which individuals have the capacity to obtain, process, and understand the basic health information and services needed to make appropriate health decisions, said Marjorie Kagawa Singer, PhD, MA, MN, RN, FAAN, Research Professor/Professor Emeritus in the Department of Community Health Sciences and the Department of Asian American Studies at the UCLA Fielding School of Public Health. She said that only about 12 percent of adults have proficient health literacy, and 14 percent of adults (about 30 million people) have health literacy below the basic level.
The vast majority of adults also lack the skills needed to manage their disease, said Kagawa-Singer. “Where are we missing the boat? In essence, everywhere,” she said. She also noted that the U.S. is a pluralistic society with citizens of many cultural backgrounds. Navigating the U.S. health care system requires being aggressive, and many cultures do not embrace or foster that trait.
“System navigation is certainly a challenge,” said Shalewa Noel-Thomas, PhD, MPH, Bureau Chief for the Cancer and Chronic Disease Prevention Bureau at the Washington, D.C., Department of Health and former Director of the Office of Minority Health and Health Disparities at the Maryland Department of Health.
She noted that the term health literacy encompasses many aspects: health systems literacy, including understanding self-care, primary care, urgent care and emergency room care, and how to access services; insurance benefits literacy, including understanding co-pays, deductibles, prior authorization, and networks; and health behavior literacy. Most patients with low health literacy need intensive support, such as help from navigators and community health workers, she noted.
For patients with low health literacy, fear, poverty, fatalism, language barriers and lack of information, lack of insurance, and false beliefs play strong roles, said Elmer Huerta, MD, MPH, Director of the Cancer Preventorium, Washington Cancer Institute, MedStar Washington Hospital Center in Washington, D.C., the first Latino National President of the American Cancer Society (2007), and a senior medical contributor for CNN en Espanol.
“We need to concentrate on the person with the tumor,” not just on tumor biology, stressed Huerta, author of several books including Confronting Cancer. “Look patients in the eye and say, ‘I'm with you all the way.’” Huerta's radio and TV programs have reached Spanish-speaking populations in the U.S. and Latin America for more than 25 years, and his Cancer Preventorium, founded in 1994, has seen more than 37,000 people—mostly poor and uninsured Latinos—for prevention and early detection. Two-thirds of people seen at the Preventorium have less than a high-school education.
Huerta told Oncology Times that receiving health information from experts they trust is crucial to improving the comprehension level of people with low health literacy. He noted that he has built up a high level of trust with the Latino population over the decades that he has been communicating health information in Spanish, and that he hears from physicians in other countries who tell him their patients are educated because they listen to him.
Agreeing on the need to build trust with all patients, including those with low health literacy, was Roundtable on Health Literacy member Lisa K. Fitzpatrick, MD, MPH, MPA, founder of Grapevine Health, an organization that uses storytelling and videos to improve health literacy at the community level. She is also a professorial lecturer at the Milken Institute School of Public Health at George Washington University, a member of the Aspen Institute Global Leadership Network, and former Medical Director for the Medicaid program of Washington, D.C. She said neighborhood residents tell her, “If I can't understand you, I don't trust you.” “Value trust. It is a currency that matters. Show up and engage where people are,” she emphasized.
Complicating the need to improve patients' health literacy is that currently there are many competing demands for physicians' attention and they are overwhelmed, said Anthony Back, MD, Professor at the University of Washington School of Medicine, Division of Oncology; Co-Director of the Cambia Palliative Care Center of Excellence; and co-founder of VitalTalk, an organization that offers evidence-based training courses on communication about serious illness to empower clinicians and institutions.
“Communication is a learned skill; it's not something you're born with,” said Back. “Physicians are poor judges of their own communication skills. Why don't they try?”
They say they don't have time, the time isn't right, they are unsure what to say, and they have had no formal training in communication. “Skills training improves communication,” he stressed, adding, “Serious illness conversations improve outcomes. This is not any more about being a ‘nice doctor.’” What training in communication skills is about, he said, is empowering physicians and building more patient trust.
Back said that physicians need to be attuned to the patient who seems to understand what is being said but actually doesn't. “Many patients try to be polite...they are scared to death,” he noted.
Communication Strategies
Among the strategies for improving cancer health communication emerging from the NAS meeting were the following.
As previously reported in Oncology Times, another NAS committee recently released a consensus report containing a sweeping new cancer control plan for the U.S. One of the recommendations of that committee is to launch and expand public, engagement, literacy, and outreach activities, starting with K-12 curricula and through technology platforms, to broaden the understanding of cancer prevention as an integral component of a healthy life course.
Peggy Eastman is a contributing writer.
|
| Therapy to Treat Drug-Resistant Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia accounts for one in five adult leukemias and is the most common pediatric cancer in the U.S. While new immune therapies have helped improve survival rates, some patients are unresponsive to existing treatment regimens. In addition, drug-related toxicities and drug resistance are rampant for these patients, spurring an urgent need for new therapy options.
Researchers from Case Western Reserve University School of Medicine have developed a new combination treatment regimen that enhances the immune system's ability to kill leukemias that do not respond to standard treatments. The regimen includes a therapeutic antibody designed to draw natural killer (NK) immune cells to cancer cells. The antibody attached specifically to acute lymphoblastic cancer cells as early as 30 minutes after treatment and remained attached for 2 days, serving as a flag to attract NK immune cells. The researchers were able to maximize the antibody's efficacy by adding a second, anti-tumor molecule to the regimen.
Results published in Cancer Immunology Research describe how the antibody attaches to a specific protein on the surface of acute lymphoblastic leukemia cells (B-cell activating factor, or BAFF-R) (2019;7(7):1106). Once the antibody attaches to a cancer cell, NK cells also attach to the antibody and this antibody acts like a bridge connecting cancer cells to NK cells, where it quickly gets to work destroying the cancer cell. The antibody connects with NK cells through a second protein commonly found on their surfaces (CD16).
The researchers, Reshmi Parameswaran, PhD, Assistant Professor in the Department of Medicine and MD/PhD student in her lab and the Department of Pathology, Yorleny Vicioso, created a new acute lymphoblastic leukemia mouse model for the study. They used mouse models with growing, drug-resistant cancer cells collected from human patients. Then, they tested treatments over the course of disease progression—starting with the antibody alone.
“If we started to treat mice with the antibody early during disease development, leukemia was almost eradicated by this treatment method; however, if treatment was administered late when the tumor had grown and established its own microenvironment, the antibody alone was less effective,” said Parameswaran, who is also a member of the Case Comprehensive Cancer Center and a St. Baldrick's Scholar.
As cancer cells grow, they secrete molecules that disrupt and confuse the body's natural immune responses. The area around an established tumor—its surrounding “microenvironment”—can contain myriad molecules that inhibit immune cells. Parameswaran's team found unusually high levels of an inhibitory molecule called TGF-beta in the bloodstreams of the mice. Closer inspection revealed that the cancer cells were secreting TGF-beta directly, which accumulated over time in their microenvironments as a defense against NK cells. TGF-beta in the microenvironment inhibit the ability of NK cells to kill cancer cells by more than half.
“There was a clear negative effect of the tumor microenvironment on natural killer cell killing capacity,” Parameswaran said. “So, we added a TGF-beta receptor inhibitor to our antibody treatment regimen.”
Using their mouse disease model, the researchers showed that the combination of these two treatments enhanced killing of acute lymphoblastic leukemia cells—even if the disease was advanced. Antibody and TGF-beta receptor inhibitor treatment increased NK cell activity against cancer cells by up to 35 percent. The researchers confirmed the combination's efficacy in mice injected with acute lymphoblastic leukemia cells from four different patients.
The combination treatment could represent a promising new regimen for late-stage acute lymphoblastic leukemia, particularly benefitting adults who are unresponsive to existing options. Data from the new study suggest the antibody, which attaches to BAFF-R on cancer cells, could be more effective in older patients.
“We looked at BAFF-R expression in a small group of 16 patients and all of them expressed this receptor. It's promising as a therapeutic avenue for late-stage disease,” Parameswaran said. “Data from larger patient sets will help us draw a definitive conclusion.”
The custom BAFF-R antibody is currently being tested as a therapy to treat autoimmune diseases and rheumatoid arthritis in two clinical trials. The TGF-beta inhibitor was recently tested in a first-in-human clinical trial for treatment for advanced-stage solid tumors. The new mouse model study provides critical preclinical data to support combining the two treatment in human trials, Parameswaran concluded.
Simultaneous Infection by Two Viruses Key to Studying Rare Lymphoma
New research has found that a rare blood cancer can be simulated in the lab only by simultaneously infecting white blood cells with two viruses typically found in the tumors. The successful creation of stable, cancer-like cells in the lab opens up opportunities for understanding the progression of this and related cancers and, perhaps, developing treatments.
Primary effusion lymphoma (PEL) is a rare blood cancer that primarily affects those with compromised immune systems, such as people infected with HIV. It is aggressive and patients typically live just 6 months after being diagnosed.
The cancerous B cells that make up PEL nearly always harbor two viruses, Epstein-Barr Virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), which are both known to induce other types of cancer. Previous research has largely failed to stably infect B cells with both viruses in the lab, the key to developing a productive model of the cancer for further research.
Bill Sugden, PhD, Professor of Oncology at University of Wisconsin-Madison, and his lab reported that the two viruses support one another (Proc Natl Acad Sci U S A 2019; https://doi.org/10.1073/pnas.1905025116). When healthy B cells are exposed to both viruses within a day of one another, a small fraction of the cells remains infected for months.
In their work, the researchers discovered a rare population of EBV- and KSHV-infected cells that outcompeted other cells in the lab, behaving much like cells from PEL tumors. This population of quickly growing cells will help researchers untangle how this rare cancer forms in the body and how viruses can trigger cells to grow uncontrollably.
“All of a sudden we now have a tool to understand for the first time: how does a lymphoma possibly arise from infection of two tumor viruses and what are those two viruses contributing?” noted Sugden, a member of the McArdle Laboratory for Cancer Research at the UW-Madison School of Medicine and Public Health.
In the past, researchers had tried to induce PEL-like behavior in B cells by infecting them with KSHV, the principal marker of the cancer. But those infections failed. Cells would slough off KSHV after days or weeks and did not continue to grow.
For Sugden, who has long studied EBV, the solution made sense: use the viruses together. After all, they're typically found together in cancer cells isolated from patients.
“Everything I know about this virus says that it will not be retained in these lymphomas unless it was doing something to contribute,” he noted.
In early attempts, Aurélia Faure, PhD, who recently received her doctorate in Sugden's lab, found KSHV better infected B cells when they were activated by inflammatory chemicals to start dividing. Still, the infections were transient.
Because EBV infection also strongly activates B cells, Faure and Sugden reasoned the virus might promote infection by KSHV. So Faure introduced both viruses to the cells, staggering infection by 1 or more days. EBV greatly increased the fraction of B cells that were infected with KSHV, although it was still limited to about 2 percent of the original population.
Most importantly, EBV allowed the cells to grow and maintain the KSHV virus stably for months. Faure found that KSHV infection was most successful when cells were infected with EBV 1 day before being exposed to KSHV. That narrow window for success is likely one reason that dual infection and subsequent development into PEL is rare in people.
While the small fraction of doubly infected B cells was often overgrown by the larger population of partially infected cells, the researchers discovered one population that could hold its own. What they termed the “fast” group of cells overgrew all others in the experiment, acting in many ways like the aggressive PEL cancer. Mitch Hayes, working with Faure and Sugden, found the cells had a form of antibody associated with PEL cells and shared patterns of gene expression in common with PEL tumors.
In all, the fast-growing population Sugden's lab developed appeared to be the first good model of PEL in the lab.
“Now we can go back with these cells and try to understand: What's the expression of EBV genes? What's the expression of KSHV genes in them that allow the cells to proliferate? What's the expression of EBV genes that allows KSHV be retained and vice versa?” stated Sugden.
He is intent on teaching other cancer researchers how to produce this useful population of growing, stably and doubly infected cells. He is also offering up the original lines of cells his lab uncovered. That community resource will drive a better understanding of how these viruses manipulate cells to form a lethal cancer. “I'm going to do anything I possibly can to build on this work so that we attract other people to work on it.”
|
Immunotherapy for Patients With Melanoma Metastatic to the Brain
Throughout his career, Hussein Tawbi, MD, PhD, Associate Professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, has been committed to medical oncology and oncology research, not only to help patients with cancer live longer, but also to develop better drugs to treat more people.
From the outset of his medical training, Tawbi also has had a general interest in improving outcomes for so-called “special populations” of patients who are not eligible for clinical trials for multiple reasons, such as renal disease or other organ dysfunction.
One specific population that is almost always excluded from clinical trials is patients with brain metastases, which is something that just never really sat well with him.
“Any patient that has evidence of tumor in the brain has traditionally been excluded from being on any systemic therapy clinical trials. But at some level that is not fair, because they also have cancer and they need to be treated,” Tawbi explained. “And that's a situation that I felt very strongly about changing.”
Recognizing that “all of the progress made in oncology is made through well-conducted clinical trials in phase I, phase II, and phase III settings,” he was eager to begin enrolling his patients in clinical trials of groundbreaking new immunotherapies for treating cancers of all kinds, including melanoma. But he quickly hit a snag.
“Up to 40 percent of the patients that I see in clinic with melanoma already metastatic to the lung or liver also have brain metastases, so it happens a lot. But, when I try to put these patients in clinical trials, most of the studies will say, ‘Sorry, your patients are not eligible. You have to treat their brain metastases first with radiation or surgery and prove that their brain is completely stable,’” Tawbi said.
The delay could be as long as 3 months, which is plenty of time for new brain metastases to develop, he noted.
“From that perspective, the question becomes ‘Why, exactly, do we have to exclude these patients?’” Tawbi shared. “In melanoma, we were very fortunate in the last 7-10 years that we've started having really effective treatments, and there really was never any reason as to why these patients with brain metastases should not be considered for those treatments,” he said.
“So we started developing studies that were specifically targeted to this population. Studies in which we take patients that have active untreated brain metastases and we try to assess the safety and the efficacy of treatments in that population,” Tawbi continued. “And that's kind of how this whole story was born. We started doing studies with targeted therapy, and doing studies with immunotherapy, to try to prove that drugs that work outside the brain may actually have an impact inside the brain as well.”
Those efforts would culminate in a single-arm, phase II study that enrolled 94 patients who received a combination of the immune checkpoint inhibitors ipilimumab and nivolumab, the results of which were published in the New England Journal of Medicine (2018; 379:722-730).
At a follow-up of at least 9 months with a median of 14 months, 26 percent of the participants in the clinical trial had a complete response, 30 percent had a partial response, and 2 percent had stable disease. What's more, the 1-year survival rate (82%) in the Tawbi-led study was more than quadruple the typical 1-year survival rate for patients with brain metastases, which is less than 20 percent.
The practice-changing study results indicate treatment with immunotherapy may be initiated right away in all patients with metastatic melanoma, including those with brain metastases historically excluded from clinical trials of the Nobel Prize-winning drugs, thus paving the way for the simultaneous treatment of brain and extracranial disease.
Not surprisingly, the groundbreaking research has earned Tawbi and his colleagues many accolades, including a 2019 Excellence in Oncology award from Oncology Times.
“It is exceptionally rewarding to be recognized for this effort, mostly because it highlights how impactful on patient outcomes our results are,” Tawbi said. “This recognition helps us shine a light on this population in need of progress—patients with brain metastases from melanoma—as well as other cancers, and provides us with additional motivation to continue working hard toward that.”
Most Important Findings
Brain metastases can damage or destroy tissue; cause intracranial pressure, fluid buildup, brain bleeds; and even block the flow of cerebral spinal fluid. Symptoms depend on the tumor location and can include headaches, seizures, loss of sight or hearing, and changes to the sense of smell and touch, among others.
From a research perspective, melanoma is appealing because it is one of the cancers most likely to metastasize to the brain, Tawbi said. One concern some had about the clinical trial, however, was that using immunotherapy to induce a response might cause inflammation in the brain, and thus cause more harm than good, he noted.
“If you treat someone with immunotherapy, you are really trying to induce an immune response, which sometimes can manifest in inflammation that can lead to swelling. And one of the first outcomes of the study was that swelling only occurred 5 percent of the time, which is very important,” he explained.
“The second most important finding in the study was that, not only was this treatment safe, but also induced response at the same rate that we see outside of the brain, so about 55 percent intracranial response,” Tawbi continued. “We were particularly pleased that about half of these responses, 29 percent, are complete responses, meaning the tumor completely disappeared.
“And, kind of the third part, was that we managed to treat those patients and they responded, but also their responses were really durable,” he added, noting, “In the last update I presented, at ASCO 2019, 87 percent of the responses had been ongoing a median follow-up of 20.6 months.”
The response to the combined immunotherapies was about 10 percent higher than with targeted therapies and also better than single-agent immunotherapy like nivolumab or pembrolizumab, which have a 20 percent response inside the brain and 35-40 percent response outside of the brain. Both results were surprising, Tawbi said.
“We always expected to lose a little bit, so we were really surprised that we didn't, and that the response inside the brain was just as good as outside the brain,” he noted. “And since the patient responses were durable, it allowed most of them to avoid additional radiation or surgery to remove their brain metastases.”
The rationale for combining the two immune checkpoint inhibitors selected for the clinical trial is that they work in two different places, or two different kinds of nodes in the immune response, Tawbi said.
“It was expected that anti-CTLA-4 would generate more T cells to recognize more antigens, and the anti-PD-1would basically unleash those T cells to do to be more effective once they tried to attack the tumor,” he explained. “So, it made a lot of sense to combine those drugs together, because they work in different places. And true enough, in patients with brain metastases, that combination was highly effective. It was also toxic, but it was highly effective.
“Based on the results of this combination outside of the brain, we decided to try it inside the brain,” Tawbi continued. “It wasn't something specific about brain metastases, so much as just the fact that we wanted to use the most effective combination that we have for this population that needs a very high rate of response.”
While some have questioned whether the immunotherapy worked in the clinical trial because the brain metastases were tiny tumors, the results show that logic is short-sighted, Tawbi said. “The median size of those lesions was actually 16 mm, and some of them were as large as 3 cm,” he explained. “So, that's one of the issues that people misconstrue, that immunotherapy only works because the tumors are small, and the reality is that is not exactly correct.”
It is also important to understand that there were two cohorts included in the study, Tawbi noted. Both patient populations had brain metastases. However, one cohort did not require steroids to treat their symptoms, while the other cohort included patients who were either symptomatic or actively using steroids during the clinical trial.
“The first cohort that we published in the New England Journal of Medicine, and now we updated at ASCO 2019, was that that population was asymptomatic and requiring no steroids. And that is really important because steroids decrease immune response,” he said. “Unfortunately, patients with brain metastases require steroids because they have headaches or numbness or weakness.”
The second cohort the researchers accrued for the phase II study included 18 patients, among whom 11 were actively using steroids. “And what we reported at ASCO was that patients who were on steroids at the time of initiation of therapy had a much lower response rate than the first cohort,” Tawbi explained.
The researchers believe that the immunotherapy is counteracted by steroids. “Checkpoint inhibitors are all about releasing the brakes on the immune system, whereas steroids are by definition the brakes on the immune system. So, at some level, it's not surprising when you put someone on steroids that immunotherapy does not work, because you are almost giving the antidote,” he stated.
“And our hope was that immunotherapy has been so effective that maybe it can be so potent as to break through the steroids and still give patients the therapeutic benefit,” he continued. “But it is a very small number of patients that were on steroids who were treated, and it seems, unfortunately, that it does not work.”
Melanoma & Beyond
Feedback has been overwhelmingly positive from the melanoma community and the general oncology community who agree that the results of the phase II study are practice-changing for all doctors who treat patients with brain metastases regardless of the anatomical location of the original cancer.
“We've observed that in our own practice. And I speak to people around the country that tell me that these results have changed the way that they treat their patients,” Tawbi related.
“Mostly that is because the general approach has been that if you wanted to treat patients with immunotherapy you had to hold off for several weeks until you fixed the brain metastases with radiation of surgery,” he said. “And then, by the time you check them again, they may have developed new brain metastases. So, sometimes it can be like you are chasing your tail.
“But with these new results, basically we have shown that you can immediately start patients on immunotherapy knowing that their brain is also going to be potentially better,” he continued. “And so that's highly impactful. And again, it really affects the way I treat my patients every day, and the way that my colleagues in melanoma, in general, treat their patients as well.”
Going forward, Tawbi said, one of the biggest research questions to tackle is: “How can we make immunotherapy effective for those patients who require steroids because of how significant their brain metastases are? Is that by bringing in new combinations of immunotherapies, or combining immunotherapy with targeted therapy, or with radiation, or maybe even considering using steroid-sparring agents? So that's definitely one line of investigation.”
The other line of investigation ahead for the researchers is determining why it is that although the combination of ipilimumab and nivolumab is very effective for the brain, up to 55 percent of patients will have high-grade, immune-related toxicities, Tawbi said.
“They are unrelated to the fact that the patient has brain metastases, but they still happen. They get hepatitis and colitis, and hypophysitis, and other significant side effects. So we're hoping to develop a new generation of immune therapies that would give us the same benefit without giving us that much toxicity. So, that's kind of the two lines of investigation we are pursuing,” he explained.
Meanwhile, Tawbi and his fellow researchers believe their approach—although maybe not the same combination of therapies for every cancer—portends therapeutic benefit for patients with brain tumors that are not exclusively metastatic from melanoma.
“Brain metastases happen in lung cancer, breast cancer, kidney cancer, and up to 30 percent of all patients with metastatic cancer in general,” Tawbi said. “So, our hope is that our results, as they are right now, and as we work with our colleagues in other cancers, may actually inspire new studies in this population with brain metastases from other cancers.”
In fact, he noted, MD Anderson has already established a Brain Metastasis Clinic, which Tawbi co-directs, and which treats patients with for brain tumors metastatic from melanoma as well as breast cancer, renal cell cancer, and more.
“We treat these patients along with radiation oncologists and neurosurgeons, and so we are applying multidisciplinary care to those patients, which allows us to innovate with the sequence of the events and the sequence of the combinations and interventions,” he said. “So I think it really is very important progress in that regard, and that we may be able to help patients beyond melanoma.”
Chuck Holt is a contributing writer.
2019 Excellence in Oncology
|
ASCO Guidelines Direct Clinical Decisions for Biliary Tract Cancer N
Is adjuvant therapy, including fluoropyrimidine-based or gemcitabine-based chemotherapy and/or radiation therapy recommended for patients with resected biliary tract cancer?
That was the clinical question which guided an expert panel assembled by ASCO to develop a set of evidence-based guidelines aimed at assisting clinical practice decision-making for patients with biliary tract cancer (BTC) (J Clin Oncol 2019;37(12):1015-1027).
Based primarily on results from a phase III randomized controlled trial, the ASCO panel recommended patients with BTC be offered adjuvant capecitabine chemoradiation therapy for 6 months, which they concluded “may be a reasonable option to address the goal of reducing the risk of local recurrence.”
Additionally, the new guidelines recommend patients with extrahepatic cholangiocarcinoma, along with a microscopically positive surgical resection margin (R1 section), may be offered chemoradiation therapy.
Finally, a shared decision-making approach was recommended by the ASCO panel of experts, “considering the risk of harm and potential for benefit associated with radiation therapy for patients with gallbladder cancer.”
The new guidelines were necessitated by a high rate of recurrence, the lack of a standard of care for adjuvant therapy, and an evidence base consisting mostly of small, retrospective studies that previously investigated treatments for BTC.
In addition to gallbladder cancer, BTC includes intrahepatic, perihilar, and distal cholangiocarcinomas, all of which involve a malignant transformation of the epithelium with biliary differentiation despite their diverse genetic makeup. Surgery and perioperative care is the typical treatment approach for these tumors. Chemoradiation therapy (CRT) is used sparingly and primarily for recurrent or metastatic disease.
BTC is found most often in the gallbladder, and depending on the stage at diagnosis, has a 5-year survival rate ranging from 2 to 70 percent. The 5-year relative survival rates for intrahepatic cholangiocarcinoma are 2-15 percent, and for extrahepatic cholangiocarcinoma they are 2-30 percent. Hilar tumors are most common and account for 60-70 percent of all cholangiocarcinomas.
And although considered relatively rare in Western countries, in 2018, there were 12,190 new diagnoses and 3,700 deaths from gallbladder cancer and extrahepatic bile duct cancer in the U.S. alone.
A Systematic Review
The primary evidence informing the new ASCO guidelines for BTC was the results of the phase III study, “Capecitabine or Observation after Surgery in Treating Patients with Biliary Tract Cancer (BILCAP),” a randomized clinical trial conducted in the U.K. (Lancet Oncol 2019;20(5):663-673).
The BILCAP study was the first positive phase III randomized controlled trial in resected biliary tract cancer. The study confirmed the benefit of adjuvant capecitabine, according to the ASCO panel, which “found no high-level evidence” to warrant recommending radiation therapy alone for patients with BTC.
From 2006 to 2014, the BILCAP clinical trial enrolled 447 patients, 223 of whom were randomized to a capecitabine group and the remainder to an observation group. Nearly half of the patients in each group underwent treatment involving their lymph nodes. About 38 percent of both groups had an R1 resection.
The primary BTC sites included 84 intrahepatic (19%), 128 hilar (28%), 156 extrahepatic CCA (35%), and 79 muscle-invasive gallbladder cancers (35%). In the intention-to-treat analysis, median overall survival (OS) was 51.1 months (95% CI 34.6-59.1) in the capecitabine group and 36.4 months (29.7-44.5) in the observation group (adjusted HR 0.81, 95% CI 0.63-1.04).
In the BILCAP trial, capecitabine was dosed at 1,250 mg/m2 twice per day during days 1-14 of a 3-week cycle for 8 cycles. The 6 months of adjuvant capecitabine chemotherapy recommended in the new guidelines for BTC should only be offered following resection, although it is fine for the dose to be determined by institutional and regional practices, the ASCO panel concluded.
In recommending patients with extrahepatic cholangiocarcinoma and R1 resection receive CRT, the ASCO panel noted how well patients tolerated radiation in the Southwest Oncology Group's phase II study, SWOG S0809 (J Clin Oncol 2015;33(24):2617-2622).
In that prospective, single-arm clinical trial of CRT, radiation was delivered at 45.0 Gy to regional and 54.0-59.4 Gy to the tumor beds of 79 patients with hilar cholangiocarcinoma (48%), distal cholangiocarcinoma (16%), and gallbladder cancer (32%). A similar rate of local recurrence and median OS occurred in the R0 and R1 subgroups, despite the latter being expected to have poorer outcomes.
The ASCO panel stopped short of recommending optimal dosing of CRT based on SWOG S0809, however, citing an underdeveloped evidence base. While the SWOG researchers only “cautiously attribute” the positive effect of the treatment on the R1 group of patients to the efficacy of adjuvant therapy, they noted.
Informing the Guidelines
In addition to the important phase II SWOG S0809 study, which the ASCO panel said “surpassed its predetermined threshold for efficacy and demonstrates the feasibility of conducting a national trial in this patient population,” important data that informed the new guidelines was gleaned from previous phase III studies of adjuvant therapy for BTC, including the Ebata, et al, and PRODIGE 12 randomized controlled trials.
Ebata, et al, enrolled 225 patients in Japan with extrahepatic cholangiocarcinoma (45% hilar and 55% distal) (Br J Surg 2018;105(3):192-202). Patients with resected bile duct cancer were randomized to gemcitabine and observation groups by lymph node status, residual tumor status, and tumor location in the phase III study titled “Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer.”
Patients received 1,000 mg/m2 of gemcitabine intravenously on days 1, 8, and 15 every 4 weeks for 6 cycles. No significant differences were observed in OS (median 62.3 vs. 63.8 months, respectively; HR 1.01, 95% CI 0.70-1.45; P=0.964) or relapse-free survival (RFS) (median 36.0 vs. 39.9 months; HR 0.93, 0.66 to 1.32; P=0.693).
Because the clinical trial by Ebata, et al, failed to enroll the intended number of patients, “it may have resulted in an underpowered analysis,” the ASCO panel concluded, despite the authors' position that the small size of their study was unlikely to have affected the results.
The PRODIGE 12-ACCORD 18 (UNICANCER GI) clinical trial (Ann Oncol 2017;28:v605-v649; suppl 5; abstr LBA29) asked if gemcitabine and oxaliplatin chemotherapy (GEMOX) would increase RFS and maintain health-related quality of life (HRQOL) in patients with a resection.
The French multicenter, open-label, randomized, phase III study included 196 patients with intrahepatic (46%), perihilar (8%), or distal (27%) cholangiocarcinoma, or gallbladder adenocarcinoma (20%). GEMOX was dosed as gemcitabine 1,000 mg/m2 on day 1 and oxaliplatin 85 mg/m2 was infused on day 2 of a 2-week cycle for 12 cycles.
At a median follow-up of 46.5 months (95% CI, 42.6-49.3 months), 126 RFS events and 82 deaths were reported, but no significant differences in RFS between the study's two arms, the time-to-definitive deterioration of global HRQOL, or OS.
“The PRODIGE 12 trial had significant imprecision around the estimate for the primary outcome of RFS,” the ASCO panel noted in the new BTC guidelines, adding, “Evidence quality (i.e., certainty) for the comparisons of gemcitabine plus oxaliplatin or gemcitabine alone versus observation was judged to be low due to these limitations.”
The new ASCO guidelines for BTC also provided evidence- and consensus-based recommendation for patients with microscopically positive surgical margins. The expert panel is anticipating results from two ongoing clinical trials “will further inform clinical decision-making for this patient population.”
The studies cited studies include the ACTICCA-1 randomized controlled trial comparing cisplatin and gemcitabine to capecitabine, and the Japan Clinical Oncology Group Study 1202 assessing treatment with adjuvant S-1 in patients with resected BTC, which the ASCO panel says “might shed light on the role of fluoropyrimidines.”
Looking forward, future research should focus on “high-risk patient subgroups and reported results for specific biliary tract subsites and/or specific molecular alterations,” say the ASCO panelists, who state collectively that they “will continue to assess the currency of these recommendations and consider the need to update this guideline on an annual basis.”
Influence On Clinical Practice
To better understand the real-world impact on clinical practices, Oncology Times asked Anton Bilchik, MD, PhD, Professor of Surgery and Chief of Gastrointestinal Research at John Wayne Cancer Institute at Providence Saint John's Health Center in Santa Monica, Calif., to share his thoughts about the new ASCO guidelines to assist clinical decision-making for patients with BTC.
Bilchik is an internationally recognized surgeon and scientist who pioneered techniques to improve staging in colon cancer and minimally invasive approaches for liver and pancreas cancer. He is trained and certified in advanced laparoscopic and robotic surgery, and also serves as an investigator on international multi-center clinical trials with more than 200 publications. He is considered one of the country's leading specialists in surgical oncology.
What is your overall opinion of the new ASCO guidelines to assist clinical decision-making for patients with BTC?
“This is very important since this is the first time guidelines have been provided for the adjuvant treatment of biliary tract cancer based on level-one data. Most trials have either been negative or accrual has not been met and therefore trials have been closed prematurely.”
Do you treat patients with capecitabine as adjuvant therapy as recommended by the ASCO panel? If so, what were the patient outcomes?
“Yes, we have. But most patients receive a combination of gemcitabine and cisplatin. Capecitabine is particularly appealing because it is mostly well-tolerated and can be given in pill form. The outcomes vary largely because biliary tract cancers include both bile duct cancers and gallbladder cancer.”
Do you agree with the recommendation that patients with gallbladder cancer and an R1 section receive chemoradiation therapy?
”Yes, it makes sense that patients with an R1 resection should receive chemoradiation to reduce the risk of local recurrence. Most of our patients receive chemoradiation if they have a good performance status.”
How important do you feel shared decision-making is in caring for this patient population?
“It is essential because these cancers mostly present late with few curative options. Furthermore, because these cancers are not that common compared with other cancers, prospective studies have been very challenging to complete, leaving decision-making often to the individual oncologist based on best judgment.”
Is there anything you think the ASCO panel should have recommended but did not, or anything else you would like to add about the new guidelines?
“I think ASCO should have discussed the potential for targeted treatment such as [trastuzumab] in HER-2 positive tumors. Also, there is a wide variation in how radiation is delivered—short course (SBIRT) versus the standard long course.”
Chuck Holt is a contributing writer.
|
| UpToDate® No abstract available |
Mogamulizumab-Kpkc (Poteligeo®)What is mogamulizumab-kpkc?
Mogamulizumab-kpkc is a first-in-class monoclonal antibody directed at the C-C chemokine receptor 4 (CCR4) expressed on the surface of regulatory T cell and Th2 cells.
Mogamulizumab-kpkc selectively binds to CCR4, a G protein-coupled receptor for chemokines involved in the movement of lymphocytes throughout the body. CCR4 is expressed on the surface of some T-cell malignancies and, through mogamulizumab-kpkc binding, results in antibody-dependent cellular cytotoxicity.
What is this approved for?
Mogamulizumab-kpkc is approved for patients with relapsed or refractory mycosis fungoides (MF) or Sezary syndrome (SS) after at least one prior systemic therapy.
What is the basis for this approval?
Mogamulizumab-kpkc was approved based on the results of MAVORIC, an open-label phase III, randomized trial in relapsed or refractory patients with MF or SS who had failed at least one prior systemic therapy. A total of 372 patients were randomized 1:1 to either mogamulizumab 1 mg/kg or vorinostat 400 mg and were stratified by disease subtype and stage. Tumor expression of CCR4 was not required for enrollment. Patients with CNS metastases and prior allogeneic transplant were excluded. The primary endpoint was progression-free survival (PFS) by investigators assessment with additional endpoints including overall response rate (ORR), duration of response, and quality of life.
PFS was significantly prolonged with administration of mogamulizumab, 7.7 months versus 3.1 months for vorinostat (HR 0.53; 95% CI 0.41-0.69, p<0.0001). ORR was 28 percent for mogamulizumab and 5 percent for vorinostat (risk ratio 23.1, 95% CI 12.8-33.1; p<0.0001) with the majority being partial responses. Main safety concerns for mogamulizumab were infusion reactions, rash, diarrhea, and fatigue. Response was not dependent on expression of CCR4 (Lancet Oncol 2018;19:1192-1204).
How do you administer this drug?
Mogamulizumab-kpkc is administered as an intravenous infusion with a 0.22 micron (or equivalent) in-line filter. It is given at a dose of 1 mg/kg over at least 60 minutes on days 1, 8, 15, and 22 of a 28-day cycle, then on days 1 and 15 of all subsequent 28-day cycles.
Are there any premedications needed?
Patients should receive diphenhydramine and acetaminophen prior to the first infusion. If an infusion reaction occurs, these should be repeated for all subsequent infusions as well as consideration for an extended infusion time.
What are the common side effects (> or =10%)?
What are the uncommon side effects (less than 10%)?
Additional side effects include hyperglycemia (9%), insomnia (9%), hyperuricemia (8%), dizziness (8%), peripheral neuropathy (7%), depression (7%), hypomagnesemia (6%), and arrhythmias (5%).
Are there any important drug interactions?
None currently studied.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
There are no known renal or hepatic dose adjustments; however, it has not been studied in severe renal or hepatic impairment.
Practical tips
What should patients know?
Patients should contact their health care provider if they experience any of the following: shortness of breath, new or worsening skin rash, and/or fever, sweats, or chills.
What else should I know about this drug?
What useful links are available?
Any ongoing clinical trials?
Clinical trials with mogamulizumab-kpkc are being conducted to investigate its place in therapy in other disease states and drug combinations. It is currently being studied alone for lymphoma or solid tumor malignancies, as well as in combination with docetaxel for non-small cell lung cancer, nivolumab for metastatic solid tumor malignancies, or pembrolizumab for relapsed or refractory lymphoma. More information is available about the clinical trials at https://clinicaltrials.gov.
KENDALL C. SHULTES, PHARMD, BCOP, is Assistant Professor at the Belmont University College of Pharmacy and Clinical Pharmacy Specialist at Vanderbilt-Ingram Cancer Center Cool Springs, Nashville, Tenn. JANELLE E. MANN, PHARMD, BCOP, is an Ambulatory Clinical Oncology Pharmacist, Washington University School of Medicine, Alvin J. Siteman Cancer Center, St. Louis, Mo., and serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor.
|
Breast Tumor Profile Fortifies Risk Gene Panel in Younger Patients
Combining classic clinical tumor characteristics with the 21-gene breast cancer recurrence score (RS) more accurately predicts which premenopausal patients may safely forego adjuvant therapy than the gene assay alone, researchers have found. Results from a pre-specified secondary endpoint analysis of data from the landmark Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx—the largest breast cancer treatment trial to date—were first reported at the 2019 ASCO Annual Meeting and published in the New England Journal of Medicine (2019;380:2395-2405).
The primary endpoint findings of the TAILORx trial, published in 2018, showed that about 70 percent of women with hormone receptor (HR)-positive, HER2-negative, axillary lymph node–negative breast cancer, the most common form of the disease, have a low enough distant relapse risk that, when guided by the RS assay, they may not require chemotherapy.
In the new analysis, hazard ratios for distant recurrence among women at high clinical risk were about 2.5-3 times higher than for those at low clinical risk, regardless of endocrine therapy, either alone or with chemotherapy. Combining classic clinical features could also be used to identify which younger patients will most likely benefit from more effective anti-estrogen therapy, the researchers said.
“With this new analysis, it is clear that women ages 50 or younger with a RS result between 16 and 20, and at low risk clinically, do not need chemotherapy,” said lead author Joseph A. Sparano, MD, Associate Director for Clinical Research at Albert Einstein Cancer Center and Montefiore Health System in New York City.
“Integration of the RS with clinical risk information could also help identify premenopausal women at higher clinical risk who may benefit from ovarian function suppression and more aggressive anti-estrogen therapy.”
Supported by the NCI, the trial was designed and led by the ECOG-ACRIN Cancer Research Group, of which Sparano serves as Vice Chair.
Study Details
Out of a total of 9,427 women with RS and clinical risk information, 70 percent were found to be at low risk if they had a low-grade tumor no larger than 3 cm, ≤2 cm and intermediate grade, or ≤1 cm and high grade. The other women were determined to be at high clinical risk of distant recurrence. Most of the patients were being treated with tamoxifen alone.
Clinical risk features were prognostic in women with an intermediate RS of 11-25 who were randomly assigned to endocrine monotherapy or combined with chemotherapy for women with higher recurrence scores.
After 9 years, the estimated rate of distant recurrence was less than 5 percent for patients 50 years of age or younger who received endocrine therapy alone and had an RS of 10 or less, regardless of clinical risk, and around 4.7 percent of low clinical risk and an intermediate RS. The estimated 9-year recurrence rate was above 10 percent among patients with high clinical risk features treated with endocrine monotherapy, and in women with a high RS who received both chemo and endocrine therapy.
Although clinical risk features added prognostic value across all groups, disease-free survival and distant recurrence-free interval rates were similar with or without chemotherapy in the entire RS 11-25 group, regardless of clinical risk. However, clinical risk alone was not predictive of chemotherapy benefits, and this proved true for two-thirds of the subjects over age 50 or older.
Editorial
“Readers may be surprised to learn that the classic prognostic markers were not directly analyzed in the 2018 article, unsurprised to learn that they contribute prognostic information, and curious as to why it took two articles in the Journal, published almost a year apart, to impart this information,” wrote NEJM Deputy Editor Dan L. Longo, MD, Dana-Farber Cancer Institute, and statistician David J. Hunter, MB, BS, University of Oxford, U.K. (N Engl J Med 2019;380:2472-2474)
The answers lie in how clinical trials are conducted and reported, and affirm the need to incorporate new research findings into practice, they explained.
On the basis of previous studies, they observed, the authors indicate that adding ovarian suppression and an aromatase inhibitor might reduce risk equivalent to that of adjuvant chemotherapy.
“Thus, practice-changing suggestions are being made on the basis of a subgroup analysis of a secondary objective in the trial, published as a follow-up to the report of the primary objective.”
“The promise of ‘precision’ medicine has collided with the rather messier world of using all available evidence to try and make educated guesses to improve patient outcomes,” according to the editorial.
“To then view this data set as the test of a single hypothesis would be wasteful of the opportunity to incorporate secondary objectives or even post hoc analyses...The presentation of additional analyses from important data sets will remain a fundamental component of evidence synthesis,” according to the commentary.
The reporting of findings beyond prespecified and primary objectives is important, and “judicious use of these data should continue to inform clinical practice,” they wrote.
Kurt Samson is a contributing writer.
|
| BIS Technology: Prevention of Cancer-Related Lymphedema
Despite advances in breast-conserving surgery, improved radiation protocols, the advent of certain biopsies, and chemotherapy regimens, breast cancer-related lymphedema remains a major source of morbidity and concern among breast cancer patients. Up to 30 percent of women treated for breast cancer develop lymphedema in one or both arms after surgery, radiation therapy, or chemotherapy. The traditional method for evaluating a patient's risk of developing lymphedema is to measure the circumference of the arm with a tape measure, but increasingly, studies have shown that this does not provide the most accurate or timely assessment of lymphedema progression.
Like many medical conditions, secondary cancer-related lymphedema develops in stages and, if caught early, progression can be prevented (Figure 1). At stage 0, lymphedema is reversible. The lymphatic system is impaired but there is not enough fluid buildup for patients to notice symptoms.
At stage I, fluid accumulation usually results in noticeable swelling and discomfort. Treatment at this stage can alleviate symptoms and sometimes reverse progression. At stages II and III, lymphedema is irreversible.
Unfortunately, the majority of cases are not diagnosed until they are already visually apparent. If changes could be found before they are visually apparent, patients could receive treatment that could prevent the condition from getting worse (Ann Surg Oncol 2018; http://doi.org/10.1245/s10434-018-6601-8).
Lymphedema Prevention
Interim clinical results from the PREVENT trial demonstrate that lymphedema could be preventable if caught at its earliest stages, before a patient experiences symptoms and begins treatment with at-home care, including appropriate compression garments. The PREVENT Trial employs bioimpedance spectroscopy (BIS) technology, which measures impedance at 256 different frequencies over a full spectrum (from 3 kHz to 1,000 kHz) and does not depend upon population-specific prediction equations to generate fluid volumes or tissue masses. Because the technique used does not assume that extracellular fluid (ECF) and intracellular fluid (ICF) are uniformly distributed, it provides a more direct and individualized measure of ECF, ICF, and total body water compartments of the body, creating significant advantages, particularly in patient populations with altered fluid homeostasis.
The PREVENT Trial is the largest, multi-site randomized controlled trial ever performed to study lymphedema prevention. The pre-specified interim analysis followed the first 508 patients enrolled in the study through 12 months of follow-up. Surveillance of women at risk for breast cancer–related lymphedema using BIS to identify early changes in ECF, when combined with immediate compression therapy, resulted in 95 percent of those women not experiencing lymphedema progression. These interim clinical results demonstrate that lymphedema is largely preventable if caught early and if treated at home using appropriate compression garments.
To catch lymphedema at stage 0 or stage I, at-risk patients must be routinely monitored during clinical assessments using BIS, which measures their L-Dex score. This score measures the fluid accumulation in a limb that is at risk for lymphedema and compares it to a healthy limb. An increase in the L-Dex score of 6.5 from a baseline value is an indicator of the development of lymphedema and, combined with clinical assessment, triggers the need for at-home intervention using compression garments (Figure 2) (Ann Surg Oncol 2019; https://doi.org/10.1245/s10434-019-07344-5). At this stage, off-the-shelf compression sleeves, which are less expensive than custom garments (often required for chronic lymphedema), are typically required for 4 weeks.
L-Dex Score History Chart
With early detection, cancer survivors can avoid facing the common symptoms of lymphedema, such as swelling, mobility issues, and hospitalization for potentially fatal infections, as well as time-consuming daily care regimens and purchasing expensive compression garments.
Results from other studies have also demonstrated that prospective monitoring utilizing the L-Dex score combined with early intervention for breast cancer patients at risk for lymphedema lowered progression to chronic lymphedema. These findings support early prospective screening and intervention for cancer patients at risk of developing lymphedema.
BIS vs. Tape Measure
The BIS device is a direct measure of extracellular fluid, whereas the tape measure simply measures the overall volume of the arm. Tape measure does not differentiate between volume gain due to fluid, muscle, or fat. BIS is sensitive to changes in lymphatic fluid, shown to detect as little as 2.4 tablespoons (36 m) of fluid differences between the arms. Although tape measurement is the most commonly used lymphedema measurement method around the world, accuracy of measurement is problematic. In starting the PREVENT Trial at multiple sites, we provided an initial half day of training in order to get accurate tape measurements for the research study and we conduct yearly fidelity visits to make sure there has been no slippage in techniques.
The PREVENT Trial interim results demonstrate that surveillance of breast cancer survivors using L-Dex should be routinely used in clinical practice and coupled with a conservative compression intervention to prevent lymphedema (Ann Surg Oncol 2019; https://doi.org/10.1245/s10434-019-07344-5).
|
Wearable Devices Show Potential for Improving Outcomes in Cancer Patients No abstract available |
The Role of Informatics in Precision Oncology
It's no surprise that health care is moving toward a future of tailored care for each person diagnosed with cancer. Precision oncology still has much room to grow, but research presented at the 2019 ASCO Annual Meeting shows great promise for realizing the vision of caring for every patient by learning from every patient. But, to drive precision oncology forward, informaticians must be engaged.
Informatician Elmer Bernstam, MD, MSE, MS, FACP, FACMI, Professor and Associate Dean for Research at UTHealth, explains the critical need for informatics to realize precision oncology's potential in personalizing care for every patient diagnosed with cancer. Here's what he told Oncology Times.
1. Why is informatics needed to realize the potential of precision oncology and how will it accelerate the transformation of cancer care?
“Precision oncology requires multiple steps from discovery to practice; each of these steps can benefit from informatics. Precision oncology may leverage a variety of patient-specific information such as behavior, preferences, and exposure history. However, for this discussion, let's focus on genomically targeted therapy.
“First, we must be able to learn what works. For example, which variants are clinically significant and what drugs effectively target the clinically significant variants? To accomplish this requires methods to analyze genomic sequencing data from individual patients. Genomic information must be combined with clinical data to identify useful associations between specific variants and outcomes such as response (or resistance) to a particular drug. Informatics can help standardize the collection of large clinical datasets. Further, routinely generated clinical data from patients' personal medical records have a great deal of potential to inform the care of patients with cancer.
“Second, to realize the promise of precision oncology as ‘standard of care’ for all patients with cancer, rather than a ‘one off’ project for each patient, data must be brought to the point of care and integrated into clinical decision-making. This cannot be done without computerized decision support. There are simply too many variables and the required information change too quickly. Today's variant of unknown significance may be an important target tomorrow. Simply tracking drug-gene associations is a formidable challenge that requires informatics.
“For example, our collaborative team from the UT Health Science Center at Houston and the UT MD Anderson Cancer Center developed an informatics tool called the Automated Identification of Molecular Effects of Drugs (AIMED) to serve as a reference for oncologists, helping to identify actionable drug-gene relationships to inform personalized treatment options for each patient.
“Finally, on a population level, informatics is the key to developing risk prediction models that adapt to changing demographics and treatment strategies for an increasingly diverse population.”
2. What areas of research presented at ASCO 2019 include the work of informatics?
“Researchers have explored various aspects of precision oncology, working towards a future where genomic tests will help identify optimal treatment options for patients, while minimizing ineffective treatments that are not likely to help. But, in order for researchers to develop these treatment options, there must be enough high-quality patient data to provide insight. Though almost 40 percent of Americans will be diagnosed with cancer, only a small minority (3-5%) of adult cancer patients actually participate in clinical trials.
“In an effort to provide clinicians and researchers optimal amounts of high-quality data and to advance cancer data sharing, a core set of data standards—minimal Common Oncology Data Elements (mCODE)—was developed and shared at the 2019 ASCO Annual Meeting. mCODE is essential in capturing and reporting characteristics, treatment, and outcomes of every patient with cancer. Electronic health records (EHRs) contain data from nearly 15 million people living with cancer in the U.S., but because not all EHRs collect data in the same format, they're often incompatible with one another. For that exact reason, cancer researchers are drastically limited in their ability to learn from patient records to later inform treatment options.
“Without compatible EHRs, data sharing is limited and, in some cases, not possible, making it difficult to share patients' medical data with doctors, hospitals, and researchers. mCODE works to combat incompatibility among EHRs by developing common data standards developed by informaticians in the oncology community. With common data standards implemented into EHRs, researchers can determine which treatments work, or don't work, for each person living with cancer.
3. There seems to be a lot of conversation around artificial intelligence's role in precision oncology. Can you speak on the relationship between informatics and AI to advance precision oncology further?
“Today's focused approach to cancer is to develop genetic risk prediction models, prevent or diagnose cancer earlier, and explore targeted treatment options for cancer. This requires genomics, proteomics. and metabolomics data being generated on clinical tumors, which is aided by artificial intelligence (AI), to classify tumors and predict aggressiveness and outcomes, therefore supporting personalized treatments.
“As people become enamored with the idea of AI driving research and providing new treatments, informaticians are working to identify important biomedical problems that can be addressed by AI. For example, many informatics groups are using AI/machine learning to improve early diagnosis of sepsis. At the American Medical Informatics Association 2019 Annual Symposium, informaticians will be gathering to discuss this approach of integrating informatics and AI to help promote precision oncology.
“Informatics helps oncologists use big data to match patients to the appropriate treatments or clinical trials. And in order to successfully implement precision oncology, informatics should be applied every step of the way—collection, understanding, and implementation—to inform the best possible treatment and care for patients.”
|
Πέμπτη 5 Σεπτεμβρίου 2019
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου