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Patient-Partnered Genomics Study Offers Insight Into Rare Cancer

Nalley, Catlin

doi: 10.1097/01.COT.0000553136.76360.ce
Opinion
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Recently reported data from the Angiosarcoma Project identified immune checkpoint inhibition as potentially actionable for angiosarcomas of the head, face, neck, or scalp (HFNS).

Launched by the Broad Institute in March 2017 in collaboration with Dana-Farber Cancer Institute, the Angiosarcoma Project is a patient-partnered genomics study. Patients are involved throughout the length of the project, including design, build, launch, and accrual.

Patient-reported data, medical records, archival tumor tissue, saliva, and blood samples are collected from individuals across the U.S. and Canada who have agreed to contribute to this study. This allows researchers to develop a comprehensive resource to facilitate discoveries for this rare disease.

“Angiosarcoma is an exceedingly rare cancer affecting about 300 patients a year in the U.S., has a high mortality rate, and has no standard of care; because of its rarity, there is a dearth of scientific discoveries that can lead to clinical impact,” said Corrie A. Painter, PhD, Associate Director of Operations and Scientific Outreach at Broad Institute of MIT and Harvard, in a statement. “It is important to develop novel approaches for working with patients who are geographically dispersed and who may never have the opportunity to participate in a large-scale prospective research effort because they have such a rare disease.”

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Building the Project

The Angiosarcoma Project (ascproject.org) was developed following the success of an initial endeavor in the metastatic breast cancer space.

“The Metastatic Breast Cancer Project was launched in October 2015 and it has been very successful from a number of different metrics, including patient enthusiasm,” Painter told Oncology Times. “Given the positive responses to this project, we wanted to extend the ability to work with patients affected with other cancers.”

The team hypothesized that they could utilize the same platform for a rare cancer and achieve the same results they saw in a major disease. And, as a survivor of angiosarcoma, Painter knew this was a very engaged community. Posting to an online support group, Painter gauged their interest in donating left over tissue and medical records to cancer research. “Within 1 hour, 90 patients expressed their desire to participate,” she recalled. “This was the rationale behind the project.”

Social media remains a critical aspect of the project. “The Angiosarcoma Working Group” on Facebook is used to communicate findings and connect with patients, according to Painter. “This group represents a mixture of people—patients, researchers, doctors, and caregivers—who are highly invested in research for angiosarcoma and have come together to work on this project.”

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Initial Findings

Data from the initial analysis were recently presented at the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival.

Researchers performed whole exome sequencing of approximately 20,000 genes on tumor and matched germline DNA. Several genes, known to be altered in angiosarcoma, were identified in the samples, including KDR and TP53, according to study findings. Of the 321 patients registered to date, 21 percent had angiosarcomas of HFNS.

“When first reviewing the data, we noticed outliers on the tumor mutation burden (TMB) graph. We also noted that all of those cases in the first data release matched patients who had angiosarcomas of HFNS,” Painter explained. “We hypothesized that the high TMB was caused by UV damage and there could potentially be a UV signature in the DNA.”

From the initial cohort of 12 patients, all three with angiosarcoma of HFNS had high TMB (10 mutations per MB) and dominant UV light signature, according to the researchers.

“Our work suggests that patients with angiosarcoma of HFNS have a high mutational burden and UV light signature, and therefore may respond to checkpoint inhibition,” Painter observed.

Given the potential impact of this finding, the research team sought to identify additional patients. Painter and colleagues found an additional 56 patients with angiosarcoma of HFNS who provided treatment details.

Of these patients, two had previously received immune checkpoint inhibitors. Both patients had refractory metastatic HFNS angiosarcoma and reported undergoing off-label anti-PD1 therapy, according to investigators. “Both had complete or near-complete responses following immunotherapy, and currently report stable or no evidence of disease.”

Angiosarcomas of HFNS represent the largest demographic of people affected by the disease, therefore, Painter noted, these initial findings could have far-reaching implications for a significant number of patients with this rare cancer.

Looking beyond this patient population, the Angiosarcoma Project has broad implications for cancer research as a whole, especially when it comes to rare diseases. “This study serves as proof of principle that patient-partnered genomics efforts can democratize cancer research for exceedingly rare cancers,” Painter noted.

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Ongoing Discovery

Painter and her team plan to continue the momentum of this project. “We are still building it out in terms of samples and sequencing them,” she noted. “We are getting ready to write up our findings. Additionally, we continue to look at the data and see what other insights we can gather.”

And their plans go well beyond the angiosarcoma space. “Based on the success of both the Metastatic Breast Cancer and Angiosarcoma projects, we have also built and launched the Metastatic Prostate Cancer Project as well as the Gastroesophageal Cancer Project,” noted Painter. “All of these have been appreciated by both the patient and scientific community. As a result we have been able to rollout an official non-profit, Count Me In (JoinCountMeIn.org).

“Our ambition is to launch projects in all major cancers and most, if not all, rare cancers as well,” she continued. “Through these projects, we are going to be able to provide the biomedical community with data that will lead to discoveries across a spectrum of cancers that have had significant barriers to get patients together or the funding to actually do the type of deep analysis that we hope to make freely available.

“It is our hope that this will jumpstart a number of different labs on their way toward making discoveries that will impact the lives of patients living with cancer both today and in the future.”

The Angiosarcoma Project and others like it underscore the important role patients play.

“Being a patient myself I can say, with certainty, that nobody cares more about the success of a project like this than the people who are directly impacted by it,” Painter noted. “As dedicated as I was as a scientist, there was an end of the day. It may have been late, but I went to sleep and didn't have nightmares about it. When you are a patient it is 24/7 and so you will do everything in your power to drive progress.

“If scientists can find more ways to include patients, I think all of us will benefit,” she concluded. “I cannot wait to see what happens when we have more established roads between scientists and patients; we are at an inflection point that is going to change everything.”

Catlin Nalley is associate editor.

Wolters Kluwer Health, Inc. All rights reserved.
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