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Five years before brain cancer diagnosis, changes detectable in blood

Immune-system activity weakens before symptoms arise

COLUMBUS – Changes in immune activity appear to signal a growing brain tumor five years before symptoms arise, new research has found.

Interactions among proteins that relay information from one immune cell to another are weakened in the blood of brain cancer patients within five years before the cancer is diagnosed, said lead researcher Judith Schwartzbaum of The Ohio State University.

That information could one day lead to earlier diagnosis of brain cancer, said Schwartzbaum, an associate professor of epidemiology and member of Ohio State’s Comprehensive Cancer Center.

The study, published in the journal PLOS ONE, focused on gliomas, which make up about 80 percent of brain cancer diagnoses. Average survival time for the most common type of glioma is 14 months.

Symptoms vary and include headaches, memory loss, personality changes, blurred vision and difficulty speaking. On average, the cancer is diagnosed three months after the onset of symptoms and when tumors are typically advanced.

“It’s important to identify the early stages of tumor development if we hope to intervene more effectively,” Schwartzbaum said. “If you understand those early steps, maybe you can design treatments to block further tumor growth.”

While widespread blood testing of people without symptoms of this rare tumor would be impractical, this research could pave the way for techniques to identify brain cancer earlier and allow for more-effective treatment, Schwartzbaum said.

Schwartzbaum evaluated blood samples from 974 people, half of whom went on to receive a brain-cancer diagnosis in the years after their blood was drawn. The samples came from Norway’s Janus Serum Bank.

Because of previous research – including her own on the relationship between allergies and brain cancer – Schwartzbaum was interested in the role of cytokines, proteins that communicate with one another and with immune cells to spark immune responses. Schwartzbaum’s previous work found that allergies appeared to offer protection against brain cancer.

In this study, Schwartzbaum evaluated 277 cytokines in the blood samples and found less cytokine interaction in the blood of people who developed cancer.

“There was a clear weakening of those interactions in the group who developed brain cancer and it’s possible this plays a role in tumor growth and development,” Schwartzbaum said.

Cytokine activity in cancer is especially important to understand because it can play a good-guy role in terms of fighting tumor development, but it also can play a villain and support a tumor by suppressing the immune system, she said.

In addition to discovering the weakening of cytokine interactions in the blood of future cancer patients, the researchers found a handful of cytokines that appear to play an especially important role in glioma development.

The results of this study must be confirmed and further evaluated before it could translate to changes in the earlier diagnosis of brain cancer, but the discovery offers important insights, Schwartzbaum said.

“It’s possible this could also happen with other tumors – that this is a general sign of tumor development,” she said.

The research was supported by the National Cancer Institute.

Min Wang, a postdoctoral fellow at Ohio State’s Mathematical Biosciences Institute, was co-lead author on the research. Other collaborators at the university were Elisabeth Root, Maciej Pietrzak and Grzegorz Rempala.

— Written by Misti Crane

Targeted Therapies Show Initial Effectiveness in Subset of Papillary Thyroid Cancer

COLUMBUS, Ohio – Two immunotherapy drugs currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of melanoma also show promise for treating a rare but aggressive form of papillary thyroid cancer.

Up to 44 percent of papillary thyroid cancer patients have a B-raf mutation that can be specifically targeted by existing cancer drugs.

The B-raf gene belongs to a class of genes known as “oncogenes,” which send signals to normal cells that cause them become cancerous. B-raf gene mutations have known roles in the development of many human cancers including melanoma, lung and thyroid cancer.

In a randomized, phase 2 multi-center clinical study, led by Manisha Shah, MD of The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), investigators tested the effectiveness of the targeted therapy drug, dabrafenib (pronounced “da bRAF e nib” and marketed as Tafinlar), given alone compared with the same drug given in combination with trametinib (pronounced “tra ME ti nib”, marketed at MeKinist) to treat a subset of advanced papillary thyroid cancer patients with B-raf mutations.

Initial data shows that both dabrafenib alone and combined dabrafenib/trametinib therapy are well tolerated by patients, resulting in a 50 to 54 percent response rate among the patients advanced BRAF-mutated papillary thyroid cancer participating in the trial.

The OSUCCC – James team presented their findings (Abstract No. 6022) today at the American Association of Clinical Oncology (ASCO) annual meeting in Chicago.

“This is an entirely new approach to treating a disease that has limited treatment options. There is no clear ‘winner’ between single- and dual-agent targeted therapy yet but the good news is that both therapy approaches resulted in positive outcomes for patients, and that gives us more treatment options to help patients with this disease,” says Shah, a medical oncologist and researcher with the OSUCCC – James Translational Therapeutics Research Program. “Targeted therapy has the potential to change the standard of care for patients affected by this rare but aggressive form of thyroid cancer.”

Researchers will continue to follow patients on this trial to determine if dabrafenib alone or dabrafenib given in combination with trametinib is more effective long term.

Study Design and Methods

For this OSUCCC – James-designed and led study, oncologists recruited 53 patients with progressive B-raf-mutated progressive papillary thyroid cancer. Patient median age was 63 and all received treatment at Ohio State, Massachusetts General Hospital, MD Anderson, University of California – San Diego or University of Chicago. Patients were randomized to receive twice daily dabrafenib alone or dabrafenib given in combination with once-a-day trametinib. All drugs are administered orally. Patients who experienced disease progression on dabrafenib alone were able to cross over into the combination treatment arm.

Collaborators in this study include Lai Wei, PhD, Lori Wirth, MD, Gregory Daniels, MD, Jonas De Souza, MD, Cynthia Dawn Timmers, PhD, Jennifer Sexton, MPH, Mamdouh Beshara, Debra Nichols, Norka Snyder, Catherine Devine, MD, Bhavana Konda, MDand Naifia Lamki Busaidy, MD.

The study received funding support from the National Comprehensive Cancer Network (NCCN) and Pelotonia, a grassroots cycling event based in Columbus, Ohio, that has raised more than $130 million for cancer research at the OSUCCC – James.

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Staff Reports