IHR Newsletter

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2 Nov

Cancer Research at the Institute for Health Research

Kaiser Permanente (KP) Colorado’s Institute for Health Research (IHR) is excited to share the recent accomplishments, insights, and future directions of our cancer focused research. Under the leadership of our Investigators, our innovative teams pursue studies that will improve cancer-outcomes for our members and the communities we serve.

The World Health Organization states, “Cancer is among the leading causes of death worldwide.” In 2020, the 5 most common cancers (by number of new cases) were breast cancer, lung and bronchus cancer, prostate cancer, colon and rectum cancer, and melanoma of the skin. (National Cancer Institute, 2020).

As significant contributors in this area, we share a sample of research projects led by our Senior Investigators Debra P. Ritzwoller,PhD , Andrea Burnett-Hartman, PhD, MPH, Heather Feigelson, PhD, MPH, our Clinical Trials team, and additional staff.

Lung Cancer

Lung cancer is a leading contributor to cancer mortality in the United States (U.S.). While survival is low, progress is being made. Thanks to new screening methods and treatments, the percentage of patients that live three years past their diagnosis has increased from an average of 19% to 31%1.

Person sitting on a CT scan machine is talking to a person in a white coat with a clipboard

Our IHR investigators are actively involved in research related to more effective diagnostic and screening approaches and detection of lung cancer and the assessment of new treatment options.

First, IHR investigators are involved in several studies related to lung nodule detection and evaluation, and screening people at high risk for lung cancer using low-dose CT scans to look for cancerous lung nodules, similar to the way mammograms screen for breast cancer.

The second is developing and testing genetic markers to find cancer earlier. Because lung cancer is highly treatable when identified at earlier stages, improving the way we screen and detect lung cancer will ultimately lower the risk of late diagnosis and improve survival rates.

PROSPR-Lung (Population-based Research to Optimize the Screening Process Lung Research Center)

Debra P. Ritzwoller, PhD, and Andrea Burnett-Hartman, PhD, MPH, are leading a multi-site $16 million grant from the National Cancer Institute. Other participating sites are KP Hawaii, Marshfield Clinic Health System, Henry Ford Health, and the University of Pennsylvania. Over the last 4 and a half years, the IHR research team has created a large scientific and data research center focused on studying how the lung cancer screening process has been implemented in real-world settings, and how patient and healthcare system factors influence outcomes such as lung cancer detection and survival. Their research is also aimed at optimizing screening processes to reduce differences in participation in lung cancer screening, which could ultimately lead to a reduction in lung cancer mortality.

The PROSPR-Lung team is also working with researchers at the Cancer Intervention and Surveillance Modeling Network and Icahn School of Medicine at Mount Sinai to help improve mathematical models used to predict lung cancer screening outcomes in the U.S.

Early Detection of Lung Cancer using cell-free DNA

Heather Feigelson, PhD, MPH, is working to adapt a genetic test (already used to help guide treatment) made by Guardant Health to screen for and identify lung cancer in its early stages. This study invites Kaiser Permanente members who are part of our lung cancer screening program to donate a blood sample at the time of their low-dose CT scan. The blood samples are tested to see if cancer is detected. If these blood tests work to detect lung cancer, it is possible that the blood test could be paired with low dose CT scans to improve the accuracy of lung cancer screening. The blood test may also provide insight into how fast tumors can grow and the best way to treat them.

Additional lung cancer studies in the IHR include:

Debra P. Ritzwoller, PhD, and her team are also involved with additional cancer diagnoses and screening studies. In collaboration with KP Southern California, KP Northwest, National Jewish Health and nine other academic sites, the Patient Centered Outcome Research Institute (PCORI) funded "Watch the Spot" study follows patients identified with a lung nodule.

Andrea Burnett-Hartman, PhD, MPH, is evaluating the impact of the Nodify XL2 test, a lung nodule blood test that could assist KP Colorado pulmonologists in their management of patients with indeterminate lung nodules (nodules that cannot be easily classified as cancer).

Duc Ha’s, MD, MAS, research highlights the importance of physical activity and exercise for lung cancer control. Duc Ha, MD, MAS, is investigating interventions to increase physical activity and exercise to improve lung cancer survivorship outcomes.

Nikki Carroll, MS, was awarded a 5-year $2.5 million National Cancer Institute (NCI) funded Research Associate grant (R50). Ms. Carroll uses the PROSPR-Lung infrastructure to study treatment and survival among people diagnosed with lung cancer based on whether they smoke and other factors.

Ovarian Cancer

While all people diagnosed with ovarian cancer are automatically eligible for genetic testing, only 30%2 of diagnosed patients in the U.S. complete genetic testing. Investigators at the IHR are working to improve those numbers.

GRACE (Genetic Risk Analysis in Ovarian Cancer)
Doctor with hair up and a clipboard is smiling at a person standing in front of them

With the GRACE study, researchers Heather Spencer Feigelson, PhD, MPH, and Larissa White, PhD, MPH, CPH, and their team, are discovering ways to increase testing for ovarian cancer.

The study provides genetic counseling and testing to KP members with a history of ovarian cancer who have not been tested. As part of GRACE, testing is also offered to any family members who might have a genetic mutation based on family history regardless of whether they are KP members. Another aspect of the study is offering genetic testing to families of KP members who have died from ovarian cancer. Knowing if a genetic mutation runs in the family provides potentially lifesaving information and options to reduce the risk of developing cancer in the future.

Breast Cancer

Ductal carcinoma in situ (DCIS), one of the more complex cancers to treat, makes up 20 to 25%3 of all breast cancers. It is a noninvasive breast cancer, but it is often treated the same way as an invasive cancer. The biology of this tumor suggests that if left untreated, it could eventually progress to invasive cancer. Therefore, patients diagnosed with DCIS typically have surgery and may receive radiation and other treatments. However, some of these DCIS tumors may never progress if left alone. This may indicate that we are undertreating some DCIS and over-treating others because we do not have all the information. Ideally, we will provide personalized treatment for these breast tumors in the future.

Molecular Markers of Risk of Subsequent Breast Cancer in Women with Ductal Carcinoma in Situ:

Site principal investigator (PI), Heather Feigelson, PhD, MPH, and her team reviewed past medical records for KP members who had DCIS. Over time, some of these members never developed an invasive cancer, while others did. The study is currently looking for changes in the DNA of the DCIS tumor tissue that predicts whether invasive cancer is likely to develop over time.

HR+ HR- Metastatic Breast Cancer Study:

In the US, ~77%4 of new metastatic breast cancers (cancers that have spread farther from where they started or to another part of the body) are hormone receptor-positive (HR+). New metastatic breast cancers that are HR+ have cells with proteins that make them more likely to respond to hormone treatments. However, little is known about adherence to treatment and overall survival for patients treated in community settings. This study, led by Debra P. Ritzwoller, PhD, will follow the diagnoses of over 20,000 members in four KP regions over a 10-year period. 

Colorectal Cancer

Andrea Burnett-Hartman’s, PhD, MPH, colorectal cancer research focuses on genetic epidemiology, screening, and early onset.

Her genetic work looks at how different combinations of genes may increase a person’s risk for colorectal cancer. One genetic study, led by the Fred Hutchinson Cancer Research Center, identifies novel genes for colorectal cancer risk as part of a large consortium of institutes named GECCO (Genetics and Epidemiology of Colorectal Cancer Consortium).

Person with gloves on is looking through a microscope

A small pilot study will offer KP Colorado members who are ages 45 to 51 years and due for colorectal cancer screening an analysis of their genes and a polygenic risk score. Polygenic risk scores give a person more information about how their combination of genes influence their risk of developing a particular health condition or disease 7, including colorectal cancer; 20% to 30%5 of the U.S. population would be considered high risk based on their polygenic risk for colorectal cancer. This study evaluates whether providing personalized risk information will motivate people to get screened. Screening reduces a person’s risk of developing colorectal cancer by finding precursor lesions before they become cancer.

Early-onset colorectal cancer, which is defined as new cases in patients under the age of fifty, has been increasing since the 1990s. Meanwhile, colorectal cancer is decreasing in people over the age of fifty because of increased screening in that age group.

To better understand this issue, Andrea Burnett-Hartman PhD, MPH, worked with gastroenterologists at Kaiser Permanente Northern California and researchers at the U.S. Department of Veterans Affairs (VA) in San Diego and University of California San Diego to summarize literature on the subject. They found that the index of suspicion for people under the age of fifty has been lower among clinicians, and patients in this age group may not consider symptoms severe enough to see their doctor. Recent changes in clinical guidelines have led to a new research project at KP Colorado that seeks to improve colorectal cancer screening in people ages forty-five to forty-nine, consistent with the updated screening guidelines.

Additional Cancer Studies

Clinical Trials

Our Clinical Trials team provides the support and infrastructure for Kaiser Permanente Colorado physician investigators, sponsors, and local research partners to conduct Clinical Trials for KP Colorado members. The Program supports both Federal and Industry-sponsored Clinical Trials for KP Colorado patients with cancer to access cutting edge therapies.

Cancer and Caregivers

Debra P. Ritzwoller, PhD, and IHR research staff are collaborating with the University of Colorado Anschutz’s Cancer Center on an intervention study that is enrolling the working-age caregivers of KP patients diagnosed with cancer. The intervention will address the stress and struggles with work and family that caregivers often experience while caring for a partner or family member receiving cancer related treatment.

KP Interregional Cancer Statistics Project

Debra P. Ritzwoller, PhD, is also working on a Kaiser Permanente-sponsored interregional cancer statistics and outcomes study that looks at the incident rates for breast, colorectal, and lung cancer within and across all the Kaiser Permanente regions and the five-year survival rates after diagnosis. The combined data will compare all Kaiser Permanente regions against national metrics.

Kaiser Permanente Research Bank

The KP National Research Bank is a collaboration across all Kaiser Permanente regions nationally funded by Kaiser Foundation Health Plan and led in the IHR by Andrea Burnett-Hartman PhD, MPH, and Heather Feigelson, PhD, MPH. The goal of the KP National Research Bank is to collect blood samples from 500,000 adult KP members and utilize them, combined with survey data and medical information, to create a state-of-the-art resource for genetic and health services research, and can support research studies targeting cancer.

Preventing All Cancer

The Connect for Cancer Prevention study funded by the National Cancer Institute collects information from people ages 40-65 who have never been diagnosed with cancer to better understand the causes of cancer and how to prevent it in the future. People are invited to join Connect from several partner healthcare systems, including KP Colorado, where Heather Feigelson, PhD, MPH, is the lead research investigator. Connect is collecting genetic, environmental, and extensive lifestyle information to discover what is driving our cancer rates. Once we know those factors, we will learn how to intervene and reduce cancer risk. For more information, please visit: https://www.cancer.gov/connect-prevention-study/.

In conclusion, the IHR’s efforts in cancer research seek to improve the lives of our members, the community, and all those touched by cancer.

Thank you for your continued support and contributions!

References

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  3. Ernster VL, Ballard-Barbash R, Barlow WE, Zheng Y, Weaver DL, Cutter G, Yankaskas BC, Rosenberg R, Carney PA, Kerlikowske K, Taplin SH, Urban N, Geller BM. Detection of ductal carcinoma in situ in women undergoing screening mammography. J Natl Cancer Inst. 2002 Oct 16;94(20):1546-54. doi: 10.1093/jnci/94.20.1546. PMID: 12381707.
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  5. Jeon J, Du M, Schoen RE, Hoffmeister M, Newcomb PA, Berndt SI, Caan B, Campbell PT, Chan AT, Chang-Claude J, Giles GG, Gong J, Harrison TA, Huyghe JR, Jacobs EJ, Li L, Lin Y, Le Marchand L, Potter JD, Qu C, Bien SA, Zubair N, Macinnis RJ, Buchanan DD, Hopper JL, Cao Y, Nishihara R, Rennert G, Slattery ML, Thomas DC, Woods MO, Prentice RL, Gruber SB, Zheng Y, Brenner H, Hayes RB, White E, Peters U, Hsu L; Colorectal Transdisciplinary Study and Genetics and Epidemiology of Colorectal Cancer Consortium. Determining Risk of Colorectal Cancer and Starting Age of Screening Based on Lifestyle, Environmental, and Genetic Factors. Gastroenterology. 2018 Jun;154(8):2152-2164.e19. doi: 10.1053/j.gastro.2018.02.021. Epub 2018 Feb 17. PMID: 29458155; PMCID: PMC5985207.
  6. Burnett-Hartman AN, Lee JK, Demb J, Gupta S. An Update on the Epidemiology, Molecular Characterization, Diagnosis, and Screening Strategies for Early-Onset Colorectal Cancer. Gastroenterology. 2021 Mar;160(4):1041-1049. doi: 10.1053/j.gastro.2020.12.068. Epub 2021 Jan 5. PMID: 33417940; PMCID: PMC8273929.
  7. National Institutes of Health. National Human Genome Research Institute (2020). Polygenic Risk Scores. Retrieved August 8, 2022, from https://www.genome.gov/Health/Genomics-and-Medicine/Polygenic-risk-scores.