Pelotonia-Funded Statewide Initiatives
Funds from Pelotonia, an annual grassroots cycling event that raises millions of dollars for cancer research at Ohio State, are helping the OSUCCC – James change the landscape of cancer care by supporting three statewide initiatives that promote early detection and better outcomes for patients with colorectal, lung and endometrial (uterine) cancers in Ohio.
Ohio Colorectal Cancer Prevention Initiative Draws to Successful Close
A five-year statewide initiative to screen newly diagnosed colorectal cancer patients and their biological relatives for Lynch syndrome has closed but will have far-reaching benefits by setting the stage for future LS screening in Ohio and around the nation.
Funded over five years (2013-18) by $4.3 million from Pelotonia, the Ohio Colorectal Cancer Prevention Initiative (OCCPI) established a 50-hospital network to accommodate screenings for Lynch syndrome (LS), an inherited genetic condition that predisposes to colorectal, endometrial, ovarian, stomach and other cancers. The LS screenings identify patients and family members who may be at risk of developing these cancers so they can take precautionary measures, including heightened surveillance (e.g., colonoscopies) for early detection.
OCCPI director Heather Hampel, MS, LGC, associate director of the Division of Human Genetics at Ohio State, says the OCCPI enrolled 3,346 newly diagnosed colorectal cancer (CRC) patients, of whom 143 tested positive for LS. She also reports that 204 of their relatives tested positive, and another 101 CRC patents were found to have a hereditary cancer syndrome other than LS.
The initiative has also resulted in six publications in prestigious medical journals, including Journal of the American Medical Association (JAMA) Oncology, Gynecologic Oncology, Gastroenterology (two articles), Family Cancer and Journal of Medical Genetics. The overall results of the study are being analyzed in preparation for publication.
Hampel and colleagues estimate the OCCPI will save about 1,000 years of life and provide about $32 million in community benefit because of the lives saved in Ohio through early diagnosis of LS and, consequently, through a reduced need for cancer treatment. “Our study findings demonstrate the need and value of screening early-onset CRC patients for LS,” Hampel says, noting that her team is working to help launch this screening approach nationally. “We believe the OCCPI can serve as a road map for other states to implement LS screening as well.”
OSUCCC – James Leads Statewide Initiative Against Lung Cancer
Recruitment continues for a statewide clinical research initiative taking aim at lung cancer, the number one cancer killer among men and women in the United States. Led by Peter Shields, MD, David Carbone, MD, PhD, Mary Ellen Wewers, RN, PhD, MPH, and Barbara Andersen, PhD, the initiative is called Beating Lung Cancer – In Ohio (BLC-IO) and is supported by $3 million from Pelotonia.
The initiative will draw upon a network of 50 hospitals around Ohio that was established by an earlier Pelotonia-funded statewide project. BLC-IO has two aims: to assess the impact of advanced gene testing and expert advice on lung cancer treatment and patient survival, and to improve smoking-cessation rates among smokers with lung cancer and their family members (assess the impact of centralized telephone counseling and provider support on smoker cessation). A three-year patient recruitment period began in March 2017.
Project leaders anticipate that more than 2,000 newly diagnosed patients with stage IV non-small cell lung cancer will enroll in BLC-IO via the community hospital network. Each enrollee will receive free testing for more than 300 genes in their cancer specimens, and the physicians who treat them will receive expert support for interpreting test results and determining treatments. BLC-IO also will provide smoking-cessation support for up to three years to all participating patients and family members.
Genomics-Driven Statewide Endometrial Cancer Research Initiative Launched
A statewide clinical cancer research project called Ohio Prevention and Treatment of Endometrial Cancer (OPTEC), which is supported by $1.25 million in Pelotonia funds, aims to recruit up to 700 women with endometrial cancer from partner hospitals across the state and screen them for Lynch syndrome (LS) and other inherited genetic conditions linked to greater risk of endometrial, colorectal, stomach and ovarian cancers.
Their tumor samples will undergo molecular profiling to identify targeted treatments personalized to each patient’s tumor characteristics. Patients identified with LS and their at-risk family members will be educated about the importance of genetic testing and cancer-prevention strategies based on their increased risk for LS-associated cancers. Those whose tumors have defective DNA mismatch repair will be considered for immunotherapy clinical trials for endometrial cancer.
OPTEC is led by David Cohn, MD, and Paul Goodfellow, PhD, with multiple collaborators from the OSUCCC – James and Nationwide Children’s Hospital Research Institute. OPTEC will conduct its LS screening with a novel one-step genetic sequencing technique developed by Goodfellow and Elaine Mardis, PhD, a geneticist at Nationwide Children’s Hospital Research Institute. Genomic profiling also will help identify patients who are most likely to benefit from new medical therapies, including immunotherapy drugs that target certain proteins.
OPTEC also is supported by a five-year, multimillion grant that the National Cancer Institute (NCI) awarded in July 2018 to principal investigators Goodfellow, Mardis and Heather Hampel, MS, LGC, for a study titled “Combined NGS Tumor-Based Detection of Germline Lynch Syndrome Mutations and Prognostic Classification of Endometrial Cancers.” The NCI grant extends research supported by Pelotonia and supports the study of nearly 1,000 additional tumors from women with endometrial cancer.
The grant will help researchers develop low-cost and highly sensitive tumor-based DNA methods to identify women with inherited forms of endometrial cancer and, at the same time, test for genetic changes useful for treatment planning. Studying DNA specimens prepared in clinically approved laboratories will make it possible to rapidly translate research findings to tumor-based testing that can be applied to all endometrial cancer patients and thus improve cancer prevention and treatment.
Additional Research Highlights
Ibrutinib Outperforms Chemoimmunotherapy in Older Patients With CLL
Results from a multi-institutional phase III clinical trial show that older patients with chronic lymphocytic leukemia (CLL) have a significantly lower rate of disease progression if treated with the newer targeted drug ibrutinib, rather than with bendamustine plus rituximab – the regimen previously considered as one of the most effective therapies for this group of patients. This study – the first head-to-head comparison between these treatments – also suggests that adding the immune-based therapy rituximab to ibrutinib does not bring additional benefits beyond those seen with ibrutinib alone. Jennifer Woyach, MD, of the OSUCCC – James, was lead author of the study, which was reported simultaneously at the American Society of Hematology (ASH) annual meeting and in the New England Journal of Medicine. Woyach says study results show that ibrutinib should be a standard of care for patients with CLL. Read more
Researchers Invent RNA Nanotech to Decorate Exosomes for Cancer Therapy
A study led by researchers at The Ohio State University College of Pharmacy and the OSUCCC – James shows that attaching antibody-like RNA nanoparticles to microvesicles can deliver effective RNA therapeutics, such as small interfering RNA (siRNA), specifically to cancer cells. Researchers used RNA nanotechnology to apply the RNA nanoparticles and control their orientation to produce microscopic, therapy-loaded extracellular vesicles that targeted three types of cancer in animal models. The findings, reported in the journal Nature Nanotechnology, could lead to a new generation of anticancer drugs that use siRNA, microRNA and other RNA-interference technologies. Principal investigator was Peixuan Guo, PhD, who is a professor in the College of Pharmacy and a researcher in the Translational Therapeutics Program at the OSUCCC – James. Read more
Single Upfront Genomic Test Improves Lynch Syndrome Detection Rates
A single upfront genomic test is more effective for detecting Lynch syndrome in colorectal cancer (CRC) patients than the traditional multiple sequential testing approach, according to clinical data reported by researchers at the OSUCCC – James. The researchers say offering this type of advanced genetic testing diagnosis could help guide and expedite treatment decisions for many patients with CRC while simultaneously identifying those who also are likely to have Lynch syndrome, a genetic condition that predisposes to colorectal and other cancers. Researchers analyzed tumor samples from 419 CRC patients using both the traditional multiple test approach and the single upfront genomic tumor-sequencing test to check for multiple mutations simultaneously. Study findings were reported in the journal JAMA Oncology. Heather Hampel, MS, LGC, was corresponding author. Read more
New Drug Harnesses Immune System to Stop Triple-Negative Breast Cancer
Scientists have identified a drug therapy target for treating BRCA-mutated, triple-negative breast cancer (TNBC), according to data published by OSUCCC – James researchers. Zhiwei Hu, MD, PhD, and colleagues reported the first evidence that a molecule called tissue factor, or TF, is highly expressed in TNBC – both on the surface of TNBC cancer cells and in most of the tumor mass. The molecule is also expressed within the inner layer of tumor blood vessels, which supply oxygen and nutrients to cancer cells and help them spread to distant organs. Additionally, the team showed that an injectable, second-generation TF-targeting therapeutic molecule is effective at targeting TNBC cells in laboratory and preclinical animal models. They reported their findings in the journal Cancer Immunology Research. Read more
Study Identifies Gene Mutation Combinations That Predict AML Outcomes in Older Patients
A study led by researchers at the OSUCCC – James identified combinations of gene mutations that predict whether an older person with acute myeloid leukemia (AML) might achieve complete remission when treated with standard chemotherapy. The researchers analyzed the AML cells of 423 patients age 60 and older for mutations in 80 cancer- or leukemia-associated genes, then used that information to classify the patients into groups that had a good, poor or intermediate outcome after treatment with standard chemotherapy. Published in the journal Leukemia, the study highlighted the extremely poor outcome of AML patients age 60 and older with current treatment approaches, but it also revealed mutation combinations that associated with patient survival. Clara D. Bloomfield, MD, was the study leader. Ann-Kathrin Eisfeld, MD, was first author. Read more
Genetic Biomarker Linked to Improved Survival in Some Brain Tumor Patients
A DNA-level biomarker called MGMT promoter methylation can help predict survival outcomes in patients with high-risk, low-grade gliomas, according to a study conducted through the NRG Oncology/RTOG collaborative clinical trials group and led by scientists at the OSUCCC – James. Data reported in the journal JAMA Oncology shows that patients with MGMT-methylated tumors are more than twice as likely to survive after combination temozolomide and radiation treatment than patients who have unmethylated tumors. Gliomas are a class of brain tumors that develop in the supportive cells that surround nerve cells in the brain. This study represented the first published data showing that MGMT promoter methylation status can be used to predict patient outcomes. Arnab Chakravarti, MD, was senior author for the study. Read more
Broad Genetic Testing for Advanced Lung Cancer May Not Improve Survival
Testing for dozens of genetic mutations in tumors of patients with a common form of advanced lung cancer does not appear to improve survival compared to routine genetic testing. A study co-authored by researchers at the OSUCCC – James used broad-based genomic sequencing (BGS) to evaluate numerous genes to identify mutations in tumors of patients with advanced non-small cell lung cancer. If a mutation is found and a drug exists to target it, BGS can help clinicians personalize and treat the disease. But questions remain about how broad-based testing, which can be costly, compares to more routine testing that focuses on one or two established, treatable genetic mutations. Carolyn Presley, MD, MHS, was first author of the study, published in Journal of the American Medical Association. She conducted the research while at Yale University in collaboration with colleagues there and at Flatiron Health. Read more
Study Identifies How EGFR-Mutated Lung Cancer Becomes Resistant to Targeted Agent
A study led by the OSUCCC – James showed how tumors fail to be eradicated by therapy in lung cancer patients treated with targeted drugs called EGFR-tyrosine kinase inhibitors (EGFR-TKIs). It also suggested a way to improve therapy to slow or prevent drug resistance. EGFR-TKIs are often used to treat lung cancers that have tumor cells with EGFR gene mutations. Patients receiving these agents often improve, but tumors inevitably recur. Published in the journal Nature Communications, this study found that in EGFR-mutated non-small cell lung cancer, EGFR inhibitors activate a gene (NOTCH3) whose protein energizes a molecule called beta-catenin, which leads to cell survival despite treatment with EGFR-TKIs. It also showed in an animal model that combining an EGFR-TKI with a clinical beta-catenin inhibitor blocked the development of treatment-resistant cells, decreased tumor burden and improved recurrence-free and overall survival. David Carbone, MD, PhD, was principal investigator.
Liquid Biopsy Can Help Predict Outcomes in Metastatic Triple-Negative Breast Cancer
A clinically relevant “liquid biopsy” test can profile cancer genomes from blood and predict survival outcomes for patients with metastatic triple-negative breast cancer (TNBC), according to research by a multi-institutional team at the OSUCCC – James, Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard. TNBC represents just 10-15 percent of all breast cancer diagnoses, but it is responsible for 35 percent of breast cancer-related deaths. Scientists have made advances in understanding genomic drivers of primary TNBC, but relatively little is known about metastatic disease because surgical tumor biopsies are rarely obtained from these patients. For this study, researchers completed what they believed to be the largest genomic characterization of metastatic TNBC derived exclusively from liquid biopsies. Daniel Stover, MD, of the OSUCCC – James, was co-first and co-corresponding author of the study, published in the Journal of Clinical Oncology. Read more
Report: Labs Differ Widely in BRCA-Testing Protocols
An international survey of genetic testing labs showed that, despite the availability of BRCA1 and BRCA2 gene testing for more than two decades, global protocols and standards are surprisingly inconsistent when it comes to analyzing cancer susceptibility genes and their many variations. A multi-institutional team led by Amanda Ewart Toland, PhD, of the OSUCCC – James, surveyed 86 genetic testing laboratories around the world to better understand their testing practices for BRCA1/2 – known cancer susceptibility genes that are linked to the types of breast and ovarian cancer passed down through families. The researchers say differences in testing mean that patients could be getting different levels of accuracy in their genetic results, based on the level of testing beyond baseline BRCA1/2 testing. Survey results were reported in the Feb. 15, 2018, edition of the journal NPJ Genomic Medicine. Read more
First-in-Human ‘Nanomedicine’ Drug Shows Promise in Solid Cancers
The OSUCCC – James is one of four cancer centers involved in testing a new “nanomedicine” agent – known as BXQ-350 while in testing – for treating advanced solid tumors, including difficult-to- treat malignant brain tumors. BXQ-350 combines a protein called Saposin C, which is naturally expressed in humans, with nanobubbles of a fat molecule called DOPS. This creates an agent that can selectively target cancerous tumor cells and kill them, largely sparing surrounding healthy tissue. These fat nanoparticles can also penetrate the blood brain barrier, which makes them particularly useful against malignant brain tumors. OSUCCC – James investigator Vinay Puduvalli, MD, notes that BXQ-350 is the first agent in this class of drugs and has properties not seen in conventional cancer treatments. He believes this research can open new doors to the treatment of malignant brain tumors and other advanced cancers. Read more
Vaccination and Testing Turning Tide in Effort to End Cervical Cancer
While cervical cancer diagnoses and related deaths are down dramatically compared to 50 years ago, Ritu Salani, MD, of the OSUCCC – James, wants to help lower them even more through education, vaccination against the human papillomavirus (HPV) that causes cervical cancer and research. Salani and the OSUCCC – James were part of a national phase I clinical trial organized by the Gynecologic Oncology Group Foundation. The study utilized a more targeted treatment for patients who experience a cervical cancer recurrence, for which the recommended treatment is chemotherapy. To make chemotherapy more effective, the study also treated patients with a PARP inhibitor. PARP is a cellular enzyme that has many functions, including the repair of DNA damage. By blocking the PARP in the cervical cancer cells from doing its job, the cancer cells can’t repair themselves, and they die. Read more
Genomic Analysis Important Even for Ultra-Hypermutated Tumors Prior to Immune Therapy
Research at the OSUCCC – James underscores the importance of genomic analysis of rare malignant tumors that are genetically unstable and have many gene mutations. The researchers analyzed the cancer genomes of nine metastatic tumors and the pretreatment primary tumor from a deceased patient with a rare form of cancer called interdigitating dendritic cell sarcoma, a disease with no standardized treatment. The samples were obtained through a body donation and autopsy study. The genomic analysis revealed that all the tumors were ultra-hypermutated (the cancer cells had more than 100 gene mutations per million DNA bases). Ultra-hypermutated cancers often respond to immune therapy, but this patient’s cancer progressed despite two courses of immune therapy and targeted agents. Principal investigator Sameek Roychowdhury, MD, PhD, says this study, published in the journal Oncotarget, shows how a partnership with patients can enable the analysis of rare aggressive cancers and possibly lead to new therapies. Read more
Old Drug May Improve Radiation Therapy for Cancer
A drug first identified 150 years ago and used as a smooth-muscle relaxant might make tumors more sensitive to radiation therapy, according to a recent study by researchers at the OSUCCC – James. Led by principal investigator Nicholas Denko, PhD, MD, the researchers found that the drug papaverine inhibits the respiration of mitochondria, the oxygen-consuming and energy-making components of cells, and also sensitizes model tumors to radiation. The scientists reported their findings in the journal Proceedings of the National Academy of Sciences of the USA. The journal includes a commentary noting that the study “represents a potential landmark in the six-decade-old quest to eliminate hypoxia as a cause for radiotherapy treatment failure.” Read more
Few Women Told by Doctor That Breastfeeding Can Reduce Cancer Risk
A survey shows that, although nearly 60 percent of breastfeeding mothers knew about the link between breastfeeding and breast cancer risk reduction, just 16 percent learned this from a medical professional. This is concerning, says study principal investigator Bhuvana Ramaswamy, MD, because women should be informed that breastfeeding can reduce breast cancer risk and improve a mother’s health. Epidemiological studies show a strong correlation between prolonged breastfeeding and reduced risk of developing triple-negative breast cancer (TNBC), an aggressive form of the disease. This knowledge is especially relevant for African-American women considering whether to breastfeed, as they are two times more likely to develop TNBC when compared with women of other ethnicities. Read more
Aromatherapy and Reflexology Ease Side Effects for Cancer Patients
A noninvasive approach using aromatherapy and reflexology can dramatically reduce pain and anxiety for women undergoing cervical radiation therapy, according to preliminary data from a clinical study underway at the OSUCCC – James. Previously reported data suggests that 40 percent of women undergoing cervical radiation therapy experience such significant pain and anxiety that they develop post-traumatic stress disorder (PTSD). For this study, researchers wanted to know if integrative medicine approaches such as aromatherapy and reflexology could reduce pain and anxiety among women undergoing brachytherapy. Lisa Blackburn, a clinical oncology nurse specialist, was principal investigator of the study, which was supported by the OSUCCC – James. Initial study results were presented at the Oncology Nursing Society’s 43rd Annual Congress. Read more
Vaping Yields No Boost to Quit Rates Among Smokers, Study Suggests
People who vape and smoke cigarettes are no more likely to drop the nicotine habit than those who just smoke, a study suggests. Researchers at Ohio State studied 617 tobacco users and found no differences in quit rates for “dual users” of both traditional and electronic cigarettes. This research provides important information for public health and medical professionals who are grappling with the role vaping might play in reducing cigarette smoking, says study senior author Mary Ellen Wewers, PhD, MPH, RN. Wewers is a professor emeritus of health behavior and health promotion and a member of Ohio State’s federally funded Center of Excellence in Tobacco Regulatory Science, for which she serves as a principal investigator along with Peter Shields, MD, deputy director of Ohio State’s Comprehensive Cancer Center. The study was published in the journal Nicotine & Tobacco Research. Read more
At-Home HPV Tests Could Be Powerful Tool for Hard-to- Reach U.S. Women
Screening women for human papillomavirus (HPV) is a promising way to detect cervical cancer early, but many at-risk women go without screening for the virus and without Pap tests that look for abnormal cells on the cervix. However, researchers at Ohio State found that mailing at-home HPV tests to hard-to-reach women may be a viable approach that could be especially helpful in such regions as Appalachia, where access to health care can be limited. The study, which appeared in the journal Sexually Transmitted Diseases, found that almost 80 percent of women who received the kits used them and sent them back to researchers for testing. About a quarter of them tested positive for a cancer-causing type of HPV. “The return rate was much higher than we expected,” says Paul Reiter, PhD, MPH, an epidemiologist with the Cancer Control Program at the OSUCCC – James. Read more
Many Women Who Choose Breast Reconstruction Are Less Satisfied Than Expected After Surgery
Many breast cancer patients undergoing mastectomy with or without immediate reconstruction mispredict future satisfaction with aspects of physical and sexual health post-surgery, according to a study published by researchers at the OSUCCC – James. Clara Lee, MD, MPP, and colleagues evaluated 96 women undergoing mastectomy for either early-stage breast cancer (stage I, II, III ductal or lobular breast cancer) or as a preventive measure. Women were 21 or older and were treated between July 2012 and February 2014 at a single-institution, multidisciplinary cancer clinic. They were asked to rate six domains of future happiness 12 months after surgery: happiness, quality of life, satisfaction with breast appearance, sexual attractiveness, breast numbness and pain. Researchers found that women who chose immediate reconstruction after a mastectomy overestimated how satisfied they would be with their appearance, whereas those who chose not to reconstruct generally underestimated future satisfaction. Full study results were published in the journal JAMA Surgery. Read more