Online First/Online Only
Articles/items published ahead of print or only online.
Wednesday, July 27, 2016
Physicians from Carolinas HealthCare System's Neurosciences Institute and Levine Cancer Institute are among the authors of a study that was accepted for publication by the Journal of the American Medical Association (JAMA).
The study, released on July 26, 2016, shows that patients with the most common form of brain tumor can be treated in an effective and substantially less toxic way by omitting a widely used portion of radiation therapy (JAMA 2016;316(4):401-409). These results will allow tens of thousands of patients with brain tumors to experience a better quality of life while maintaining the same length of life.
Anthony L. Asher, MD, FACS, Medical Director at Carolinas HealthCare System's Neurosciences Institute and the senior author on the report, and as well as Stuart H. Burri, MD, Chairman, Department of Radiation Oncology at Levine Cancer Institute, began their research on this subject over 10 years ago in Charlotte, North Carolina. Along with Paul Brown, MD, at Mayo Clinic, they spearheaded an international, multi-institutional, randomized trial that will ultimately improve the standard of care for patients with a specific type of brain tumor, brain metastases, by reducing the toxicity of their treatment without reducing the effectiveness.
Typical therapies for these types of brain tumors include surgery, whole brain radiation therapy, and focused radiation, also known as stereotactic radiosurgery. "We discovered that whole brain radiation added to focused radiation in the treatment of brain metastases – in other words, cancer that travels to the brain- reduces the number of new brain tumors over time; however, patients receiving the whole brain radiation had significantly more difficulties with memory and complex thinking than patients who only had the focused radiation," said Asher.
"Whole brain radiation patients also reported worse quality of life compared with patients who only received the focused radiation," added Burri. "Interestingly, the data showed that the addition of whole brain radiation produced no improvement in survival."
According to the American Cancer Society, in 2016, there will be approximately 1.7 million new cancer cases diagnosed in the United States. Almost one in four of those patients (about 400,000) will experience spread of their cancers to the brain. In contrast, 300,000 and 240,000 patients will be newly diagnosed with breast and primary lung cancers, respectively, each year. "Brain metastases are not only extremely common, they are also a major source of disability in society," said Asher. Because of their location, these tumors often produce severe neurological symptoms, such as headaches, weakness or problems with speech and information processing, thereby compromising both daily function and quality of life in cancer patients.
According to Asher, there are two primary objectives in cancer care: to improve survival and to maintain or improve quality of life for patients.
"The first and highest rule of medical care is 'do no harm,'" said Asher. "Consistent with that obligation, when it isn't possible to extend survival with various therapies, it's absolutely essential that we work to reduce or eliminate any possibility that quality of life will be compromised by treatments. Another way to state that principle for cancer care, is that when two cancer therapies produce similar survival, it's important to understand which therapy offers patients a better quality of life."
In this study, although whole brain radiation decreased the number of new brain tumors over time, its addition to focused radiation interestingly did not result in a survival benefit over focused radiation alone. Furthermore, whole brain therapy was associated with considerably worse quality of life.
"In the past, clinicians who treated patients with brain tumors seldom used sophisticated techniques like neurocognitive tests to evaluate patients' daily function in response to various therapies," said Burri. "Without those tests, we might have incorrectly concluded that whole brain radiation was a better option for patients because it made their scans look better, at least in the short term. However, the data from our study shows that clinicians can no longer simply rely on the results of traditional lab tests or scans to assess the value of care; we have to understand the total impact of cancer therapies on our patients."
Asher and Burri emphasize that the real importance of this study is its potential to make us think differently about what really matters in cancer therapy.
The trial authors concluded that the benefit of adding whole brain radiation was outweighed by its risks in patients with one to three newly diagnosed brain metastases. This is a very relevant finding, as over 200,000 patients still receive whole brain radiation in the United States each year, and the majority of patients with brain metastases have a limited number (typically three or less) of brain lesions. The study authors now recommend that patients with one to three brain metastases should no longer receive routine whole brain radiation therapy, and should be treated with focused therapy alone to better preserve cognitive function and quality of life.
"Having the research published in JAMA is validation of more than a decade of work," said Burri. "It is deeply satisfying to have developed an important scientific project, work in close collaboration with other investigators to obtain support from the National Cancer Institute, then carry the to carry the trial to completion with publication of impactful results in one of the leading medical journals in the world."
Asher and Burri are now working on a new method of focused therapy for tumors that have spread to the brain that combines radiation and surgery. The technique was pioneered at Levine Cancer Institute and they are looking to expand and further validate the approach with the National Cancer Institute.
Tuesday, July 26, 2016
Inherited mutations in genes that function to repair DNA may contribute to metastatic prostate cancer more than previously recognized, according to a study published in the New England Journal of Medicine (doi: 10.1056/NEJMoa1603144).
Though infrequent in the general population, inherited mutations in specific types of DNA repair genes, such as BRCA1 and BRCA2, are known to predispose to prostate cancer. However, the rate of such mutations in men with metastatic prostate cancer previously was unknown.
The study revealed that more than 10 percent of men with aggressive prostate cancer that has spread outside of the prostate have inherited mutations in DNA repair genes — more than four times the rate of the general population and more than twice the rate of men with localized prostate cancer. Men with such mutations could benefit from targeted treatment already approved for ovarian cancer patients with these mutations, such as PARP inhibitors or platinum drugs.
Peter Nelson, MD, a member of the Human Biology, Clinical Research and Public Health Sciences divisions at Fred Hutchinson Cancer Research Center and senior and corresponding author of the study commented: "The result is surprising and important for men with prostate cancer as this information may prioritize certain therapies. It is also important for family members as they may have inherited a gene that predisposes them to developing one of several types of cancer and heightened awareness could enhance early detection and treatment. These findings present a compelling argument for updating prostate cancer guidelines to include germline DNA testing as a part of standard care for men with metastatic prostate cancer."
Nelson is also a professor of medical oncology at the University of Washington School of Medicine and an oncologist specializing in therapies for early- and late-stage prostate cancer, pathology and genome sciences at Seattle Cancer Care Alliance (SCCA).
Key results of the study found that 11.8 percent of men with metastatic prostate cancer, regardless of age or family history of prostate cancer, have deleterious germline mutations in one of 20 DNA repair genes surveyed. Men with metastatic prostate cancer were five times as likely to have these inherited mutations in DNA repair genes as the general population. In particular, men with advanced prostate cancer had an 18 times higher risk of carrying a BRCA2 mutation than men without prostate cancer.
"We were excited to learn how high the percentage of inherited DNA repair gene mutations is in men with metastatic prostate cancer because of the potential benefits of genetic testing. We already know a lot about some DNA repair genes such as BRCA2, but for others we are just beginning to understand how germline mutations contribute to prostate cancer risk and selection of optimal therapy," said Colin C. Pritchard, MD, PhD, Associate Professor in the Department of Laboratory Medicine, and Associate Director of the Genetics and Solid Tumors Laboratory at the University of Washington School of Medicine is the first author of the study. "As these men consider getting tested it is important to note that not all DNA repair genes are the same, and clinical genetic testing requires specialists to ensure appropriate counseling, accurate mutation detection, and results that are correctly interpreted and communicated."
The project pooled results from 692 men with metastatic prostate cancer included in seven case series across several institutions, including Fred Hutch and the University of Washington through support from StandUp2Cancer and the Prostate Cancer Foundation. Each site conducted independent screening of mutations in 20 DNA repair genes using next-generation sequencing assays.
As mutations in some DNA repair genes predispose to other types of cancer, including breast, ovarian and pancreatic, family members of metastatic prostate cancer patients with inherited mutations may be offered genetic testing, counseling and enrollment in research studies, if appropriate.
Dr. Heather H. Cheng, MD, PhD, Assistant Professor of Medical Oncology at University of Washington and Assistant Member in the Clinical Research Division at Fred Hutchinson Cancer Research Center is also a coauthor on the study, and is leading a new Prostate Cancer Genetics Clinic at the SCCA to advise men with prostate cancer about genetic testing and how results may help tailor their treatment options.
An important strength of these findings is that men included in the study were not chosen due to family history of prostate cancer or age, and different genetic screening assays produced the same percentage of men with inherited mutations.
Tuesday, July 19, 2016
Overweight or obese women who lost weight through diet or a combination of diet and exercise also significantly lowered levels of proteins in the blood that help certain tumors grow, according to a Fred Hutchinson Cancer Research Center study published July 14 in Cancer Research (doi: 10.1158/0008-5472.CAN-16-0399).
The study measured three proteins that are known to enhance tumor-related angiogenesis – the formation of blood vessels that feed tumors and enable them to grow. It was intended to see how cancer-promoting proteins changed when overweight, sedentary, postmenopausal women lost weight through diet or diet and exercise over the course of a year. The study enrolled 439 healthy women (they did not have cancer), placing each participant in one of four study arms: calorie- and fat-restricted diet; aerobic exercise five days a week; combined diet and exercise; and control (no intervention).
Study data found that women in the diet arm and the diet and exercise arm lost more weight and had significantly lower levels of angiogenesis-related proteins, compared with women in the exercise-only arm and the control arm.
The authors said that it is known that being overweight and having a sedentary lifestyle are associated with increased risk for developing certain cancers, but the reasons for this relationship are not clear.
This study shows that weight loss may be a safe and effective way to improve the "angiogenic profile" of healthy individuals, meaning they would have lower blood levels of cancer-promoting proteins. Although the researchers cannot say for certain that this would impact the growth of tumors, they believe there could be an association between reduced protein levels and a less favorable environment for tumor growth.
Thursday, July 14, 2016
While active surveillance is often recommended for patients with nonaggressive prostate cancer to reduce unnecessary treatment, the challenge for clinicians is to monitor and distinguish early-stage tumors from advanced cancers. A team of scientists led by researchers from Roswell Park Cancer Institute, Buffalo, N.Y., have demonstrated photoacoustic imaging (PAI) may be an effective tool for more accurately viewing and monitoring prostate cancer. The new research has been published in the June 2016 issue of the Journal of Biomedical Optics (doi:10.1117/1.JBO.21.6.066019).
PAI is an emerging noninvasive imaging modality that has not yet been used in clinical settings. Using PAI, this team of scientists focused a laser light on prostate cells and then "listened" using ultrasound technology to see how a dye attached to a specific prostate cancer marker, PSMA, reacted to the light waves. They chose to study this technology's use in imaging prostate cancer, as the prostate can be imaged in situ. PAI of these prostate cells, the researchers found, enabled good discrimination between cells with and without the cancer marker.
"This proof-of-concept study demonstrates that this technology may allow for real-time monitoring of prostate cancer in patients during the course of active surveillance. For patients with more aggressive disease, the technology could offer more precise targeting of biopsies to confirm the need for definitive therapy," says senior author of the study Kent Nastiuk, PhD, Assistant Professor of Cancer Genetics and Genitourinary Cancers at Roswell Park. "This technology offers the potential to confirm the initial prostate cancer diagnosis, guide biopsies and monitor tumor volume—which is currently not measureable—for improved case management and treatment decision-making."
Friday, July 8, 2016
A single breath may be all it takes to identify the return of lung cancer after surgery, according to a study authored by University of Louisville Researchers and posted online by The Annals of Thoracic Surgery (doi: 10.1016/j.athoracsur.2016.04.068).
Exhaled breath contains thousands of volatile organic compounds (VOCs) that vary in composition and pattern depending on a person's health status. A subset of four VOCs—called carbonyl compounds because of their carbon base—have been discovered in the exhaled breath of lung cancer patients. Being able to identify this lung cancer "signature" through a simple breath test has emerged as one of the most promising ways to diagnose the disease. Now the test is being used to monitor for disease recurrence.
Erin M. Schumer, MD, Victor van Berkel, MD, PhD, and colleagues from the University of Louisville analyzed breath samples collected before and after surgery from 31 lung cancer patients and compared their carbonyl VOCs levels with samples from 187 healthy patients.
The researchers found a significant decrease in overall carbonyl VOC levels following surgery; in fact, three of the four carbonyl VOCs normalized after surgery, matching levels in the control group.
"The rapid normalization of almost all of the four compounds after surgery provides strong evidence that they are directly produced by the tumor environment," Schumer said. "This study confirms that the technology is accurate."
Lung cancer is the leading cause of cancer death. The American Cancer Society estimates that more than 224,000 Americans will be diagnosed with lung cancer this year, and more than 158,000 lung cancer patients will die—that translates to 433 lung cancer deaths per day in the United States.
Schumer said those grim statistics underscore the need for early detection, "We hope that breath analysis will allow us to diagnose patients with primary or recurrent lung cancer long before they suffer from symptoms, when we have more options for treating them, giving them the best chance for cure."
Currently, lung cancer patients are followed after surgery with chest computed tomography (CT) scans, which can be inconvenient, expensive, and expose the patient to radiation. "We hope that the breath analysis can serve as the primary screening tool for cancer recurrence and a CT scan ordered only if the breath test suggests that there has been a change," van Berkel said.
The process of breath analysis is relatively simple. The patient blows a single breath into a specialized balloon. The balloon is then connected to a pump that pulls the breath over a small microchip that is smaller in size than a quarter, trapping the chemicals. The microchip is sent to the lab, where the chemicals are analyzed within hours. Breath collection can be performed in the doctor's office.
The pump is reusable; the balloon, microchip, and lab test together cost around $20, all supporting the increasing acceptance of breath tests as a cost-effective, easy-to-perform, non-invasive and rapid option for the diagnosis of lung cancer.
"The great potential with breath analysis is detecting lung cancer at any point, both as a primary screening tool and to follow patients after disease has been treated," van Berkel said. "The technology is pretty robust. Our next step is getting approval from the FDA."