Published in the January 2013 Newsletter

The ECOG-ACRIN Young Investigator Symposium, a mentoring program for promising new talent, took place in conjunction with the full ECOG-ACRIN 2012 Fall Group Meeting in November. Now in its 12th year, the Symposium exposes selected young clinical investigators to cooperative group research opportunities early in their careers and provides a forum for them to present their research in a formal manner and obtain feedback. Their oral presentations bring interesting ideas and novel approaches of young scientists from across a variety of disciplines to the attention of the ECOG-ACRIN community. While attending the Group meeting, the selected investigators are given access to the education sessions for clinical professionals, and they have many professional networking opportunities. At the 2012 Symposium, eight young investigators, chosen by Joseph A. Sparano, MD, Program Chair, and Bruce J. Giantonio, MD, ECOG-ACRIN Executive Officer, gave oral presentations and discussed their research.

Two Symposium presenters were honored with awards of distinction for their research—one in the clinical research category, and the other in the translational research category. The awards of distinction are a tradition of the Symposium, started by ECOG in 2001 and now part of ECOG-ACRIN.

The 2012 ECOG-ACRIN Young Investigator Symposium Award of Distinction for Clinical Research was presented to Stefan K. Barta, MD, MS, MRCP (UK), Assistant Professor of Medicine at the Albert Einstein College of Medicine and the Montefiore-Einstein Center for Cancer Care (Bronx, NY), for his research project “Prognostic Factors in AIDS-related Lymphomas – A Pooled Analysis of 1546 Patients.” Barta has been involved with ECOG clinical trials since his fellowship training; his home institution has been an active institutional member of the Group since 1978.

The 2012 ECOG-ACRIN Young Investigator Symposium Award of Distinction for Translational Research was presented to Mark E. Burkard, MD, PhD, for his research project “Targeting Polyploid Breast Cancer via Potassium Channel Inhibitors.” Burkard is an Assistant Professor of Medicine at the University of Wisconsin Carbone Cancer Center (Madison, WI), an active institutional member of ECOG since 1976. Burkard’s research expertise is in the area of chemical biology—in particular, on the control of human cell division. His career goal as a researcher is to develop extensively validated biomarker-driven therapeutic strategies for breast cancer. He has been involved with ECOG since joining his home institution in 2008.

About Stefan Barta’s Research: Non-Hodgkin lymphoma (NHL) is the most common HIV-associated cancer in the developed world. Barta and his team evaluated risk factors associated with HIV-related NHL, as well as HIV disease itself, to assess their respective influence on outcomes in the largest published cohort of HIV-positive patients treated for NHL. “Despite remarkable advances in outcomes for this special patient population, there are few randomized controlled trials that define an optimal approach for the treatment of HIV-associated NHL,” Barta explains, “An important example is the role of rituximab, a monoclonal antibody directed against CD20. Although overwhelming evidence supports its use in immunocompetent patients with B-cell NHL, the only randomized controlled trial in the HIV-positive population showed no benefit.”

It was the lack of comparative data that motivated Barta and his team to perform a systematic review to identify all prospectively performed clinical trials in HIV-associated NHL, extract patient-level information from the related databases, and perform a pooled analysis of the collected data. Their goal was to assess the influence of HIV-, lymphoma-, and treatment-specific factors on outcomes. Data were presented at the 2012 meetings of the American Society of Clinical Oncology1 and the American Society of Hematology,2,3 and a manuscript is in development.

Barta and colleagues found that adding information about the status of HIV disease to other well-established risk factors improved the ability to predict overall survival in patients with HIV-associated NHL. “We created a score, the AIDS-related Lymphomas-International Prognostic Index, that more accurately predicted overall survival than other existing scores in patients treated in the rituximab era,” Barta states. His team plans to expand the current patient database by continuously updating follow-up information from existing patients.

Additionally, the researchers aim to capture data in newly diagnosed patients with HIV-associated NHL treated by several American and European cooperative groups, such as the ECOG-ACRIN Cancer Research Group; the AIDS Malignancy Consortium (AMC), an NCI-sponsored clinical trials group; the Groupe d’Etude des Lymphomes de l’Adulte (GELA); and the Italian Cooperative Group on AIDS and Tumors (GICAT). Doing so will enable the researchers to detect evolving trends in treatment paradigms and outcomes, as well as long-term complications of treatment that might occur in this population.

Barta’s research project was supported by a Young Investigator Award from the Conquer Cancer Foundation of the American Society of Clinical Oncology.

About Mark Burkard’s Research: With the goal of developing a novel therapeutic strategy, Burkard and his team identified a new biomarker and then screened for gene targets. They identified a subset of cancers that contain three or more sets of chromosomes—the biomarker. Such cancers are termed “polyploid.” Burkard explains, “We hypothesized that polyploid cancers would have to work harder to deal with the big genome, offering an ‘Achilles heel’ we could target.” His group determined that such polyploid tumors comprise 14% of all breast cancers, cutting across hormone receptor-positive, HER2-positive, and triple-negative subtypes.

Burkard’s laboratory screened 2319 genes to identify those that were required for the growth of polyploid cells, but not normal cells; the screening yielded several potassium channels. The findings suggest that potassium channels could potentially be useful therapeutic targets to treat polyploid cancers without disrupting the proliferation of normal cells. Currently, his group is evaluating chemicals for lead compounds. Burkard acknowledges that selectivity inhibition of potassium channels may be a challenge. “We are looking for compounds that turn off nonvoltage-gated channels to avoid cardiac effects,” he says.

Important contributions to the work were made by Amy Fothergill, MD, and Sara Holmstrom, BS. Funding for the project was provided by the Mary Kay Foundation, the American Cancer Society, and the University of Wisconsin Carbone Cancer Center.

1 Barta SK, Xue X, Tamari R, et al. A pooled analysis of 1,144 patients with HIV-associated lymphoma: assessment of lymphoma-, HIV-, and treatment-specific factors on clinical outcomes. J Clin Oncol. 2012;30(suppl):8005. View the abstract.

2 Barta SK, Xue X, Wang D, et al. A pooled analysis of 1,546 patients with HIV-associated lymphoma: assessment of lymphoma-, HIV-, and treatment-specific factors on clinical outcomes. Presented at: 54th Annual Meeting of the American Society of Hematology. Atlanta, GA; December 10, 2012 [abstract 3682]. View the abstract.

3 Barta SK, Xue X, Wang D, et al. ARL-IPI — a new prognostic score for AIDS-related lymphomas in the rituximab era. Presented at: 54th Annual Meeting of the American Society of Hematology. Atlanta, GA; December 8, 2012 [abstract 1564]. View the abstract.