Researchers at Dana-Farber Cancer Institute and Brigham and Women’s Hospital have transitioned Profile®, one of the nation’s most comprehensive personalized medicine initiatives in cancer, to next-generation sequencing and have launched new clinical investigations supported by Profile data.

“Next-generation sequencing reveals much greater information about the drivers of individual cancers and potential targeted therapies for our patients,” said Barrett J. Rollins, MD, PhD, chief scientific officer at Dana-Farber Cancer Institute and a Profile study leader. “Our expanded platform also will generate discoveries across a greater number of cancers.”

New Findings and Clinical Investigations

At the American Society of Clinical Oncology (ASCO) 2013 Annual Meeting, Profile team members presented a poster that summarized the study and outlined the value of enterprise-wide mutational profiling in cancer research. Compared with many other cancer genetic studies, Profile captures information across all cancers. This approach has resulted in unexpected findings, including identification of lower-frequency mutations not associated with certain cancers in the past.

“We’ve already begun to make some interesting observations with Profile,” said Philip W. Kantoff, MD, chair of the Executive Committee for Clinical Research at Dana-Farber Cancer Institute.

Several clinical investigations currently supported by Profile data are designed to help inform the development of potential new drug targets or biomarkers. One of these studies is comparing mutations in patients with aggressive testicular cancer who did not respond to chemotherapy and succumbed to the disease with testicular cancer patients who were successfully treated with chemotherapy. The other study is using Profile data to search for mutations that may affect how the immune system responds to cancer by initially evaluating those that correspond with the presence or absence of an immune response in melanoma patients with lymphocytic infiltration.

Benefits of Next-generation Sequencing

Profile’s first phase, based on a genotyping platform called OncoMap, screened for the presence of 471 mutations in 41 genes known to be implicated in cancer development and growth. The study’s second phase uses OncoPanel, a targeted exome sequencing panel that spans 305 genes and detects mutations, insertions and deletions, copy number changes, and some rearrangements.

Since Profile was launched nearly two years ago, every Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC) patient has been offered the opportunity to participate in the study. Today, more than 15,000 patients have been enrolled in Profile. Enrollment in Profile will continue to be offered to every DF/BWCC patient and will soon be extended to patients at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Results from the study will further populate a database being accessed by researchers leading new studies and clinical trials.

“This is an extremely valuable structured knowledgebase for our researchers, enabling them to search data in numerous ways to support current studies and to propose new ones,” said Laura MacConaill, PhD, scientific director of Profile, in the Department of Pathology at BWH.

Clinical and Research Collaboration

Sequencing is performed in the Center for Advanced Molecular Diagnostics (CAMD) in the Department of Pathology at Brigham and Women’s Hospital, led by CAMD Director Neal Lindeman, MD. Gene selection for Profile’s OncoPanel was made in collaboration with DF/BWCC oncologists, based on potential diagnostic, clinical, prognostic, or hereditary value.

“Clinical and research collaboration has been a significant part of our decision-making process,” said Lindeman.

“The Profile team solicited input from DF/BWCC oncologists to include screening for areas that they believe may be relevant for their patients’ care, such as helping to place more patients on clinical trials. We also have provided documentation for a select number of patients placed on clinical trials based on results seen with Profile,” said Lindeman.

Launching Profile has required tremendous commitment across many scientific, clinical, and operational areas at both Dana-Farber Cancer Institute and Brigham and Women’s Hospital. Surgical oncologists, medical oncologists, pathologists, research nurses, patient care coordinators, and many others are collaborating in this effort.

“Profile is a wonderful example of how we are all working together to keep our patients at the forefront of cancer treatment and research,” said Monica Bertagnolli, MD, chief of Surgical Oncology at Brigham and Women’s Hospital and a member of the Profile steering committee. “By developing this program, we are optimally prepared to adopt important new treatment discoveries as they become available and to continue to serve as a leader in cancer discovery and research.”

Evaluating Whole Exome Sequencing

Profile’s efforts dovetail with other Dana-Farber/Brigham and Women’s Cancer Center projects using whole exome sequencing. One of these projects, led by OncoMap developer Levi Garraway, MD, PhD, includes whole exome sequencing of thoracic, breast, colorectal, and prostate cancers, as well as sarcomas, and is designed to determine whether this technology may be useful in a clinically relevant timeframe.

“Ultimately, we want to better understand how information gleaned from larger-scale sequencing can best serve oncologists in practice and help guide clinical decision making, including enrollment in clinical trials,” said Garraway.

Article provided by BWH Department of Marketing and Planning.