The approach, titled the angiosarcoma project (ASCproject), is a partnership between patients with angiosarcoma, their support systems, and researchers at the Broad Institute of MIT and Dana-Farber Cancer Institute, as well as a nonprofit research initiative called Count Me In.2 The project produces and publicly delivers clinically annotated genomic data on tumor and germline specimens on an ongoing basis.
“This work was only possible with our patient partners,” senior author Nikhil Wagle, MD, an institute member at the Broad, a medical oncologist at Dana-Farber, and assistant professor at Harvard Medical School, and director of Count Me In said in a press release. “The scientific insights they’ve helped generate have shed new light on the poorly understood roots of angiosarcoma, which urgently needs new treatment options for patients.”
Project leaders created a social media working group in order to connect patients with angiosarcoma and supporters online and invite them to aid in shaping the project’s outreach strategy. With feedback from these individuals, the ASCproject team built an online portal (ascproject.org) that allowed patients to join and provide their medical history and tumor or blood samples for DNA testing.
Observing 227 patients who had received care for angiosarcoma at 340 different clinical institutions and had fully consented to the study as of September 30, 2018, researchers highlighted the importance of online platforms to overcome the issue of geographic isolation, which has traditionally constrained large-scale studies of these rare cancers. Those who participated in the project ranged from newly diagnosed patients to long-term survivors, and the elapsed time between primary angiosarcoma diagnosis and ASCproject enrollment ranged from 5 days to 41 years.
“The participants in the ASCproject have signed up in the hopes that this will help people down the road,” co-first author Corrie Painter, associate director of operations and scientific outreach for the Broad Cancer Program and associate director of Count Me In, said in a press release. “We are grateful that in the midst of their own diagnosis, they wanted to do their part to help prevent the suffering of other patients.”
Using acquired medical records and tumor samples from the involved patients and institutions, whole exome sequencing (WES) of 47 tumors revealed recurrently mutated genes, including KDR, TP53, and PIK3CA.PIK3CA-activating mutations were found to be predominately in primary breast angiosarcoma, which suggests a novel therapeutic rationale for this patient population according to the researchers.
Additionally, angiosarcoma of the head, neck, face, and scalp (HNFS) was correlated with a high tumor mutation burden (TMB) and a dominant ultraviolet damage mutational signature, which indicates that for the subset of participants with HNFS, ultraviolet damage might be a causative factor and that immune checkpoint inhibition could be advantageous. Moreover, a review of medical records showed that 2 participants with HNFS angiosarcoma were administered off-label anti-PD-1 therapy and had experienced noteworthy responses, which draws attention to immune checkpoint inhibition as a potential therapeutic avenue for HNFS angiosarcoma.
“Findings like this can really open up the doors in terms of how we think about genes in tissue-specific contexts for cancer tumorigenesis,” Painter said. “We never would have had that insight without this data.”
The new data and potential therapeutic strategies identified within this study have afforded clinicians the opportunity to further explore the development of new clinical trials. As a part of the Count Me In initiative, a growing number of patient-partnered projects in different cancers are being assembled. Furthermore, the ASCproject specifically highlights the powerful approach that patient-partnered projects may offer for other patient populations that are currently undergoing study challenges through conventional mechanisms.
“It feels amazing to know that I and others in the patient community helped fuel these new discoveries,” Jim Chapdelaine, a guitarist and Emmy Award-winning recording musician enrolled in the project, said in a press release. “I hope for a cure one day, but this study helps open scientific doors and we hope that people will now walk through them.”
Data from the project has been publicly released at https://www.cbioportal.org and additional data continues to be released.
1. Painter CA, Jain E, Tomson BN, et al. The Angiosarcoma Project: enabling genomic and clinical discoveries in a rare cancer through patient-partnered research. Nature Medicine. doi:10.1038/s41591-019-0749-z.
2. Patient-partnered research finds clues about a rare cancer’s genetic roots [news release]. Dana-Farber Cancer Institute. Published February 10, 2020. dana-farber.org/newsroom/news-releases/2020/patient-partnered-research-finds-clues-about-a-rare-cancer-s-genetic-roots/. Accessed February 12, 2020.