Dr. Ruth Etzioni, a biostatistician in Fred Hutchinson Cancer Research Center’s Public Health Sciences Division, has received a five-year National Institutes of Health grant to advance the science of cancer surveillance by developing, validating and deploying a scalable, automated approach for identifying cancer recurrence.
Currently, the Surveillance, Epidemiology and End Results Program, or SEER, provides extensive information regarding cancer diagnosis and some data regarding primary treatment and survival, but it does not collect information on metastatic cancer recurrence. The National Cancer Institute, which oversees the SEER registries, has identified this absence as a critical gap in cancer surveillance. Metastatic breast cancer patients and advocacy organizations have also called on the NCI to fill in these data holes by counting them in.
“Cancer registries are very broad brush,” said Etzioni, regarding SEER. “They try to capture an unbiased snapshot of the population by tracking incidence, survival, mortality and trends over time. But the data collection is all built around a cancer diagnosis, not progression or recurrence. The infrastructure was not designed to collect that data. Right now, the registries are a glass half full.”
Etzioni’s new grant will focus on filling up that glass by leveraging both medical claims and patient-reported outcomes to fill in the gaps in metastatic breast cancer recurrence data.
“We propose to focus on breast cancer due to its prevalence and burden in U.S. women and will build on the extensive expertise of our study team in breast cancer outcomes and recurrence ascertainment,” she said, adding that the grant will build on existing efforts by Fred Hutch epidemiologists Drs. Kathi Malone and Christopher Li to learn more about breast cancer survivorship.
In the first, two-year phase of the grant, Etzioni will use records from the Puget Sound SEER Registry’s Fred Hutch-housed Cancer Surveillance System, which tracks cancer diagnoses in 13 Washington state counties. Etzioni and her team will cull stage 1–3 breast cancer cases from the database then utilize electronic health records, claims data and patient-reported outcomes to fill in the missing recurrence information.
Etzioni’s team will then develop an algorithm that can be used to predict metastatic recurrence, validating its accuracy against a subset of the CSS cohort, which has collected real-time recurrence data from collaborator Swedish Cancer Institute.
Funding for the first phase is approximately $905,000. Funding for the second phase, which will extend over three years, is contingent on the progress of the first two years. The proposed budget is just over $2 million.
In that second phase, Etzioni and her team will use their newly created algorithm to identify metastatic breast cancer recurrence within the Kentucky Cancer Registry, yet another part of SEER, validating the algorithm’s accuracy against gold-standard recurrence data gleaned from the electronic health records of the University of Kentucky.
Etzioni said she believes she can develop a tool that can be deployed on a large scale and be scalable across SEER registries.
She also believes the multiple collaborations will set the stage for future research partnerships.
“There’s a national effort to expand collaborations across sites that house valuable data for cancer research,” she said. “We very much want to build bridges and be a part of that effort.”
In addition to Puget Sound and Kentucky payers and providers, Etzioni has tapped technology partner Sage Bionetworks, a nonprofit based at the Hutch, to create a direct-to-patient app to help facilitate patient-reported outcomes.
“Sage Bionetworks has deployed dozens of mobile apps for population health,” said Etzioni, adding that their technology will enable researchers to capture, manage and integrate patient data without sacrificing confidentiality.
“Folding recurrence data into the cancer registry is critical to improving cancer surveillance,” she said. “These data are necessary for understanding the burden of cancer and studying the effectiveness of cancer treatments outside of controlled clinical trials. This grant is a key step forward to making this vision a reality.”
— Diane Mapes / Fred Hutch News Service
Nutritional epidemiologist Dr. Marian Neuhouser on Oct. 1 became head of the Cancer Prevention Program in the Public Health Sciences Division at Fred Hutch. She replaces acting program head Dr. Johanna Lampe, associate director of the PHS Division, who assumed that role after Dr. Polly Newcomb stepped down from the position in early 2016.
“I am thrilled and honored to lead the Cancer Prevention Program,” she said. “Cancer prevention is critical to reducing the overall morbidity and mortality of cancer and it saves millions of health care dollars. The Fred Hutch Cancer Prevention Program is one of the strongest in the nation; our faculty’s innovative research has the potential to reach millions of people to reduce the incidence of cancer around the globe.”
Neuhouser joined the Hutch as a staff scientist in 1998 and later joined the member- track faculty. Since 2011 she has been a full member of the Cancer Prevention Program, the first such National Cancer Institute-funded program in the U.S.
Neuhouser’s research focuses on the role of nutrition and energy balance (calories consumed versus calories burned) in cancer prevention and survivorship, particularly breast and prostate cancers. She also studies ways to improve methods of diet and physical-activity assessment and the extent to which biological markers of food intake can improve upon measures of self-report, such as keeping a food journal or filling out a food questionnaire — methods that are known to have substantial measurement error.
At the Hutch, she is the scientific adviser for the Nutrition Assessment Shared Resource within the Cancer Prevention Program, which makes it possible for investigators without nutrition training and expertise — or who don’t have the time and funding — to incorporate state-of-the-art dietary data-collection methods in their research studies.
She is principal investigator or co-investigator of multiple National Institutes of Health-funded grants and contracts ranging from controlled-feeding trials to large, population-based studies, including those focused on special populations such as minorities, the elderly and people experiencing health disparities.
Neuhouser has authored more than 275 peer-reviewed publications and a dozen book chapters related to dietary-assessment methods, energy balance, diet and health, and cancer prevention.
She is past president of the American Society for Nutrition and a member of the American Association for Cancer Research, the Academy of Nutrition and Dietetics and the American Society for Preventive Oncology. Neuhouser co-chairs the SWOG Prevention and Epidemiology Committee and has also served on scientific committees of the National Academy of Sciences Engineering and Medicine, and she was a member of the 2015 Dietary Guidelines Advisory Committee.
She is also a member of the core faculty of the Graduate Program in Nutritional Sciences and is an affiliate professor of epidemiology in the University of Washington School of Public Health.
— Kristen Woodward / Fred Hutch News Service
Five cross-disciplinary research groups involving scientists from Fred Hutchinson Cancer Research Center, University of Washington School of Medicine and Seattle Cancer Care Alliance — Fred Hutch’s clinical care partner — have received $100,000 awards from Fred Hutch-based Seattle Translational Tumor Research, or STTR, to develop new precision-medicine approaches for leukemia and cancers of the bladder, ovary, prostate and breast.
Below is a summary of the new projects.
Drs. Roland Walter of Fred Hutch and Brent Wood of UW/SCCA will test novel antibodies that recognize cancer cells in patients with acute myeloid leukemia, or AML, and simultaneously recruit healthy immune cells within the patient to kill their cancer.
Antibodies can either have anti-cancer properties on their own or they can be used to deliver a toxic payload to cancer cells while leaving normal tissue unharmed. In AML, an aggressive tumor of white blood cells, most antibody-based treatments have focused on a protein called CD33. One antibody (gemtuzumab oxogamicin, or GO) that delivers a toxic payload has been found to prolong survival in a subset of patients, validating this treatment approach. Unfortunately, GO is ineffective for many patients, so there is ample room for improvement in CD33-directed therapies.
In an earlier study of 29 AML patients, Walter and Wood found that their cancer cells also universally produce a variant of CD33 which, they hypothesize, could serve as a drug target with “untapped therapeutic potential.” They have now developed antibodies that recognize this CD33 variant and now seek to test whether these antibodies could provide and improved AML treatment approach.
Drs. Andrew Hsieh of Fred Hutch and Bruce Montgomery of UW/SCCA are using their STTR funding for a study that aims to understand why certain bladder cancers respond to chemotherapy while others don’t.
In the past 25 years, the Food and Drug Administration has approved only two classes of drugs to treat bladder cancer, including platinum-based chemotherapy, which damages cancer DNA. This treatment induces complete responses in up to 40 percent of patients with localized cancer and up to 10 percent of patients with advanced disease.
With this grant, the researchers aim to shed light on why platinum therapy works in some patients but not in others. Montgomery and Hsieh suspect, based on their previous research, that response to platinum treatment may have to do with defects in DNA-repair genes, which make the cancer exceptionally sensitive to the therapy.
In this study, they plan to analyze genetic material from several groups of bladder cancer patients, including “exceptional responders,” to evaluate markers of DNA repair that may help predict which patients may respond best to platinum therapy.
Dr. Christopher Kemp of Fred Hutch, together with Drs. Elizabeth Swisher and Barbara Goff of UW/SCCA, will focus their project on identifying abnormal genomic signatures unique to two specific forms of ovarian cancer. Their goal is to develop precise, targeted therapies for this disease, which is the fifth leading cause of cancer death in the U.S.
Unfortunately, there are only a few targeted agents approved for the treatment of ovarian cancer, and none are curative. A major barrier to successfully translating basic ovarian cancer research findings from the lab to the clinic is the lack of accurate models of the disease that can be used to test potential drugs. To address this need, the researchers have developed a unique set of patient-derived ovarian cancer cells that have been proven to retain the characteristics of the original cancer. They’ve also developed a highly accurate, high-throughput screening platform that can test simultaneously hundreds to thousands of gene targets or drugs.
In this project, they will use these tools to find novel, targeted agents for precision treatment of ovarian cancer that they hope to test in patients within the next two to three years.
Drs. Peter S. Nelson and Ruth Etzioni of Fred Hutch and Dr. Eva Corey of UW will pursue combination drug treatments in avatar models of advanced prostate cancer in which human prostate cancer cells are engrafted and allowed to grow in mice. Such preclinical models of late-stage prostate cancer have the potential to greatly speed the drug-development process and ensure that the results will accurately mirror the clinical responses seen in human patients.
In treating prostate cancer, the sequential delivery of single agents, one after another, predictably results in eventual drug resistance. In contrast, the simultaneous use of combinations of drugs has been shown to overcome treatment resistance and eliminate disease.
Use of avatar models allows researchers to quickly and efficiently test combinations of drugs. Ultimately, they plan to use these models to test chemo cocktails that circumvent treatment resistance and result in better responses. Promising drug combos will then be tested in human clinical trials.
Drs. Kevin Cheung and Peggy Porter of Fred Hutch, together with Drs. Savannah Partridge of UW and Habib Rahbar of UW/SCCA, will harness the power of an advanced form of magnetic resonance imaging, or MRI, together with technology for creating lab-grown organiods, or mini tumors, to discover new cancer biomarkers and test promising new therapies.
MRI not only helps find tumors, but advances over the past decade also allow the technology to tease out their distinctive features, such as cancer aggressiveness and risk of recurrence. This is made possible by advanced imaging known as “dynamic contrast-enhanced MRI,” or DCE-MRI, which uses the injection of a contrast agent to reveal the physiology of living breast-tumor tissue. This information can be used to predict whether patients will benefit from existing targeted treatments. However, extrapolating to new biomarkers and therapies from these imaging data is challenging.
To bridge this gap, the researchers will pair this imaging with cell-based experiments by creating a biobank of breast tumor organoids, which are derived from cancer cells obtained at the time of initial diagnosis. These mini tumors are then stored, much like sperm and eggs are banked, and cataloged according to their unique physiological features as revealed by MRI. Because the researchers can expand the number of organoids in the lab, they can ask many questions to discover new breast cancer biomarkers and test promising therapies.
If the researchers identify new proteins that can be targeted with therapeutic drugs, they predict their concept could lead to a clinical trial within five years — first to use the organoid biobank to test drug candidates and then to identify breast cancer patients who are most likely to benefit from the therapy.
A focus on collaboration
STTR is a multidisciplinary effort of physicians and scientists from Fred Hutch, UW Medicine and SCCA. Their primary goal is to translate laboratory sciences into the most precise treatment options for cancer patients.
Each year, STTR’s granting program, made possible by philanthropic support and funding from UW Medicine, accelerates groundbreaking, innovative research with a strong focus on collaboration across disciplines and research institutions.
This seed funding has provided pilot data for successful National Institutes of Health-funded projects, enabling its faculty members to advance their novel research.
— Kristen Woodward / Fred Hutch News Service