Fox Chase Researchers Study Tumor Characteristics and Next-Generation Sequencing as Markers for Immunotherapy Response

PHILADELPHIA (August 28, 2020)—In a recently published study, researchers at Fox Chase Cancer Center and Temple University investigated whether the use of next-generation sequencing and primary tumor characteristics could help better predict the efficacy of immunotherapy.

Next-generation sequencing refers to a number of different modern sequencing technologies that allow for quicker and cheaper methods of sequencing DNA and RNA in the tumors of patients.

“We’re doing a lot of molecular profiling on melanoma tumors and when someone has an initial biopsy of a melanoma we have unique pathological characteristics of the tumor,” said Jeffrey M. Farma, MD, FACS, author on the study and co-director of the Melanoma and Skin Cancer program at Fox Chase.

“The goal of this project was to correlate the initial characteristics of the biopsies of the initial melanoma in patients with advanced melanoma who then either had recurrence or metastatic disease and then received immunotherapy,” he added

Farma worked on the study with lead author Kimberly Loo, MD, a recent graduate of the Temple University Lewis Katz School of Medicine and a former Surgical Oncology Research student at Fox Chase, as well as several other Fox Chase researchers.

The study consisted of a cohort of 67 patients who received immunotherapy for recurrent or metastatic melanoma and for whom primary tumor biopsies and pathology reports were available. Farma said researchers looked at a retrospective database of these patients and identified several interesting correlations.

“One interesting finding involved the initial tumors that had lymphovascular invasion, where the melanoma cells were invading the blood vessels under the microscope. We think of that as a high-risk feature when we see it initially. We were able to correlate that condition with patients who actually have a response to immunotherapy. These patients were more likely to have this lymphovascular invasion in their primary tumor,” said Farma.

Additionally, the study allowed researchers to correlate patients who had the NRAS gene mutation, which is not currently a targeted gene in immunotherapy, with those patients who were more likely to respond to immunotherapy. NRAS was the first oncogene identified in melanoma. Farma said it is not yet clear why these associations exist and that it could warrant further study on a larger scale.

“Here we only have set defined tumor characteristics and a smaller patient population. This is a potential predictive tool that, if we correlated in a larger series, maybe we could predict whether a person is more or less likely to respond to immunotherapy in the future,” said Farma.

The study, “Primary Tumor Characteristics and Next-Generation Sequencing Mutations as Biomarkers for Melanoma Immunotherapy Response,” was published in the journal Pigment Cell & Melanoma Research.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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