Posted September 16, 2013
Dr. Anil K. Sood, University of Texas MD Anderson Cancer Center
Dr. Malcolm Pike, University of Southern California
Dr. Michael Birrer, Massachusetts General Hospital

Drs. Anil K. Sood, Malcolm Pike, and Michael Birrer Ovarian cancer is the deadliest of female reproductive cancers. One of the reasons for this is the inability to detect the disease early - in far too many cases, by the time the cancer is diagnosed, the tumor has already spread beyond the ovaries. The American Cancer Society estimates that in 2013 approximately 22,240 women will be diagnosed with ovarian cancer in the United States and 14,030 women will die of the disease.

While researchers forge forward in their vital effort to find a cure and to develop tools for early diagnosis, an award mechanism recently created by the Ovarian Cancer Research Program (OCRP) seeks to foster a unique approach in the fight against ovarian cancer. The Department of Defense OCRP Outcomes Consortium Development Award was created in fiscal year 2012 (FY12) to bring together teams of talented researchers focused on discovering what distinguishes the small subset of ovarian cancer patients who become long-term survivors.

Sadly, the overall survival of women with ovarian cancer has not changed appreciably over the last three decades. Despite this dismal reality, a minority of these patients become long-term survivors - defined by the program as those who have survived at least 10 years from initial diagnosis. However, very little data has been collected from long-term survivors of ovarian cancer. The OCRP Outcomes Consortium Development Award represents a new approach that seeks to characterize the biology and genomics of tumors belonging to long-term survivors, as well as identifying lifestyle factors that affect carcinogenesis and therapeutic response in these patients. The knowledge gained through this largely unexplored area has the potential to yield insights that will lead to increased survival.

In line with the OCRP's goal to support innovative, high-impact research, by design the award will not fund work that merely focuses on specific molecular pathways or genes, but rather on work specifically geared toward identifying and understanding predictors of disease outcomes in ovarian cancer patients. To maximize potential benefits, the Outcomes Consortium Development Award is designed to foster collaborations across multiple institutions and include leading ovarian cancer researchers and consumer advocates. To accomplish this, the award is executed with a two-stage approach: an initial Development Award that enables the consortium to lay the groundwork for the research project, including proof of concept, and a second award that will support the full execution of the project.

As part of Ovarian Cancer Awareness Month 2013, the OCRP has chosen to highlight the three recipients of the FY12 Outcomes Consortium Development Awards and their unique approaches to understand the features associated with long-term survival.

Looking at the Big Picture

The ideal consortium will take a comprehensive approach to studying long-term ovarian cancer survivors. The three consortia that received the FY12 Outcomes Consortium Development Awards are made up of top-notch research teams seeking to integrate biological and genomic signatures of ovarian cancers with information on treatment outcomes and lifestyle. Each consortium brings its own set of resources and focus area in an effort to identify predictors of long-term survival to enable tailored therapies that maximize patient survival and quality of life.

Dr. Anil K. Sood: Consortium to Study Long-Term Survivors of Ovarian Cancer

Accounting for 50 percent of all ovarian tumors, serous ovarian cancer is the deadliest of all ovarian cancers. Two broad tumor categories arise in serous ovarian cancers: high-grade tumors that develop rapidly and are relatively responsive to chemotherapy, and low-grade tumors that grow more slowly and are largely resistant to chemotherapy. Dr. Anil K. Sood, at the University of Texas MD Anderson Cancer Center, has assembled a consortium that includes five universities that seeks to understand long-term predictors in women with serous ovarian cancer. Over the past several years, the consortium has already used the Cancer Genome Atlas to identify genomic markers associated with long-term survival. Using data collected over the past 15 years, the researchers will assess the power of biobehavioral and sociodemographic characteristics to predict long-term survival. They will also identify treatments and side effects that correlate with long-term survival. Given that high- and low-grade serous tumors differ molecularly, each will be analyzed separately.

Dr. Malcolm Pike: Multidisciplinary Ovarian Cancer Outcomes Group

Dr. Malcolm Pike, at the University of Southern California, is also interested in serous ovarian cancer, but his consortium will focus exclusively on the high-grade form for which less than 20 percent of diagnosed women survive past 10 years. Dr. Pike's team of researchers has already established a history of working together as members of the Ovarian Cancer Association Consortium. Their goal is to uncover the characteristics of the 20 percent - a combined analysis of their tumors, the treatments they've received, and the patients themselves - that contribute to their long-term survival. The consortium plans to collect clinical records, pathology reports, tumor tissue specimens, and epidemiological data from over 400 long-term survivors and over 400 moderate (5-7 years from initial diagnosis) survivors. Should they be awarded the full consortium, 600 short-term (2-4 years) survivors and 200 moderate-term and 200 long-term survivors would be added. According to Dr. Pike, doing so would create the largest set of samples of long-term survivors ever assembled. Using this formidable resource, they will compare molecular and genetic profiles, immune response, surgical outcome and recurrences, as well as lifestyle and psychosocial factors between the different survival groups.

Dr. Michael Birrer: The Genomic, Epigenomic, and Psychosocial Characteristics of Long-Term Survivors of Ovarian Cancer

Another useful database is the one created by the Gynecologic Oncology Group (GOG), with 391 participating institutions and over 3,300 registered patients. Dr. Michael Birrer at the Massachusetts General Hospital plans to utilize the database to discover what separates long-term survivors of ovarian cancer from other patients. Genomic features (such as miRNA and methylation patterns) will be compared between long- and short-term survivors, as will immune responses. Pairing the genomic and immune data will provide a more reliable predictor of long-term survival than either alone. The GOG also collects data on quality of life, with which Dr. Birrer and colleagues imagine the possibility for markers indicative of quality of life. Lastly, the robust GOG infrastructure will allow any results to be quickly disseminated among the many participating clinicians, and the production of a genomic database that will be made available to other researchers.

Hope for Long-Term Survival

Curing ovarian cancer will require vast resources both material and creative. By focusing on long-term survivors of ovarian cancer, we can hope that the OCRP Outcomes Consortium Development Award will give rise to new insights that will benefit ovarian cancer patients being treated today and help more become survivors tomorrow.

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