Translational & Transformational Research
Barriers to understanding how cancer works are also being lifted at the Dorothy Sipkins Lab, where Gaia Cantelli, PhD, a postdoctoral fellow in the DCI Hematologic Malignancies & Cellular Therapy research program, is figuring out how acute lymphoblastic leukemia (ALL) cells, which can’t breach the blood brain barrier, enter the central nervous system. Central nervous system metastasis is characteristic of all subtypes of ALL.
“What we’ve uncovered with our current research is a new model (pathway) for these cells to enter the central nervous system (CNS) and cause paralysis and other CNS symptoms,” said Cantelli, who was awarded by DCI in the translational research category for her abstract Acute Lymphoblastic Leukemia Cells Hijack a Neuronal Pathfinding Mechanism to Invade the Central Nervous System. “This is an absolutely huge problem in the clinic both in terms of pediatric patients and adult patients that has a huge impact on patient survival and quality of life.”
In the mechanism that Cantelli described, the acute lymphoblastic leukemia (ALL) cells migrate into the central nervous system along vessels that passage directly between vertebral or calvarial bone marrow and the subarachnoid space.
“Future studies may reveal that this unique ALL trafficking pathway is involved in normal immune surveillance or inflammatory processes,” she wrote in her abstract. “Exploring the interactions between normal and malignant immune cells and these vascular scaffolds may thus reveal multiple points of intervention to treat CNS invasive processes.”
Wei Huang, MD, PhD, a second-year postdoctoral fellow in the Nelson Chao Lab in the DCI Hematologic Malignancies & Cellular Therapy research program, also received a translational research award. In her abstract — Fecal Microbiota Transplant to Restore the Recipient Microbiota Effectively Attenuates Graft-Versus-Host Disease in Mice — she explained the important role that gut microbiota play in intestinal homeostasis (stability) and outcomes after stem cell transplantation.
“Post-transplant loss of microbiota diversity in patients has been associated with increased infections, graft-versus-host disease, disease relapse and treatment-related mortality,” Huang wrote. “Case studies suggest that fecal microbiota transplant may helped restore the microbiota, suppress T-cell responses in graft-versus-host associated organs, and improve (ameliorate) graft-versus-host disease.”
Huang, who came to Duke after earning her MD in China, reflected: “When I was an intern in the hospital, I noticed that a lot of the patients who went through bone marrow transplantation, although it saved their lives, had complications and very poor quality of life. We want to find new solutions to this disease and improve the quality of life of these patients.”
Improving Patient Outcomes
Patient outcomes were also the focus of a research project by Daphna Spiegel, MD, MS, a trainee in the Joseph Salama Lab in the DCI Radiation Oncology and Imaging research program. She received a presentation award in the clinical research category for her work on Long-term Outcomes of Nonoperative Management for Locally Advanced Rectal Cancer in the Veterans Health Administration.
Her research team found that patients who underwent chemoradiation but didn’t undergo surgery and achieved a clinical complete response rate had similar overall survival and disease-specific survival compared to patients who underwent chemoradiation plus surgery and had a pathologic complete response.
Fumiko Chino, MD, won the other presentation award in the clinical research category, for her abstract Healthcare Disparities in Cancer Patients Receiving Radiation: Changes in Insurance Status after Medicaid Expansion under the (Affordable Care) Act.
Chino, a trainee in the Junzo Chino Lab in the DCI Radiation Oncology and Imaging research program, compared insurance status in cancer patients receiving radiation before and after Medicaid expansion under the Affordable Care Act.
“What we found is that the Affordable Care Act really did work to reduce un-insurance rates for patients and this means so much for cancer patients because we know that un-insurance leads to worse outcomes for cancer,” she said, adding that Medicaid expansion significantly decreased the un-insurance rates of cancer patients receiving radiation.
States that didn’t expand Medicaid, she noted, appeared to have healthcare disparities that were not found in expanded states.
The population science research awards were given to Julia Butt, PhD, a research scholar in the Meira Epplein Lab, and Andrea Sitlinger, MD, a hematology-oncology fellow in the Yousuf Zafar Lab — both part of the DCI Cancer Control & Population Sciences research program that aims to reduce the cancer burden in DCI’s catchment area.
In her project, Antibody Responses to Streptocuccus Gallolyticus Proteins in a Colorectal Cancer Cohort Consortium, Butt’s team was able to reproduce an association of antibody responses to the Streptococcus gallolyticus subspecies gallolyticus (SGG) pilus protein Gallo2178 with a risk of developing colorectal cancer.
“More detailed analysis will help to identify risk factors for antibody responses to SGG infection and to specify how long before diagnosis antibody responses to the infection might serve as a marker for colorectal cancer development,” explained Butt.
Andrea Sitlinger, MD, presented on Insurance Design and Out-of-Pocket Costs: A Comparison of Oral and Intravenous Treatment for Chronic Lymphocytic Leukemia. A cancer patient’s out-of-pocket costs for intravenous versus oral chemotherapy can vary with their insurance plan. While 43 states have enacted laws to mandate cost-sharing parity between oral and IV chemotherapy out-of-pocket costs, Sitlinger revealed that, in the case of CLL patients taking the commonly prescribed CLL treatments bendamustine/rituximab (IV) or ibrutinib (oral), there was little evidence these laws actually lowered their costs.
“In the Affordable Care Act, the maximum out of pocket cost was over $7,000 in 2017,” she said. “We found that patients receiving either bendamustine/rituximab (IV treatment) or ibrutinib (oral) reached their maximum annual out-of-pocket caps in approximately one month.”
Her research team found that drug costs (more than professional fees, lab and imaging fees) contributed most to patients reaching these caps.
“Over the years there’s been a shift in insurance to move more and more costs to patients,” said Sitlinger, pointing out the possible consequences of this financial toxicity, including bankruptcy and non-adherence to their medications. “Other methods need to be explored for reducing patients’ financial burden from these novel yet expensive therapies.”
With no shortage of ideas, the retreat wrapped up with a poster session — 81 in all — sparking discussion into the night about the latest advancements in cancer science, treatments, and care and what comes next.