The Angiosarcoma Project (ASCproject) is an initiative enabling US and Canadian patients to remotely share their clinical information and biospecimens for research. The project generates and publicly releases clinically annotated genomic data on tumour and germline specimens on an ongoing basis. The researchers reported in a letter published in the Nature Medicine that this patient-partnered approach has catalyzed an opportunity to discover the aetiology and potential therapies for patients with angiosarcoma.
Despite rare cancers accounting for 25% of adult tumours, they are difficult to study due to the low incidence and geographically dispersed patient populations. The study team led by Nikhil Wagle of Count Me In, The Broad Institute of MIT and Harvard, Dana-Farber Cancer Institute, and Brigham and Women’s Hospital, Harvard Medical School in Boston, MA, US assessed whether a patient-partnered research approach using online engagement can overcome these challenges.
They focused on angiosarcoma which has an annual incidence of 300 cases in the US. Over 18 months, 338 patients registered for the ASCproject, which comprises a large proportion of all patients with angiosarcoma.
Whole-exome sequencing of 47 tumours revealed recurrently mutated genes that included KDR, TP53, and PIK3CA.
PIK3CA-activating mutations were observed predominantly in primary breast angiosarcoma, which suggested a therapeutic rationale.
Angiosarcoma of the head, neck, face and scalp (HNFS) was associated with a high tumour mutational burden (TMB) and a dominant ultraviolet damage mutational signature, which suggested that for the subset of patients with angiosarcoma of HNFS, ultraviolet damage may be a causative factor and that immune checkpoint inhibition may be beneficial. Medical record review revealed that two patients with HNFS angiosarcoma had received off-label anti-PD-1 therapy and had experienced exceptional responses.
The study team concluded that this proof-of-concept study demonstrates that empowering patients to directly participate in research can overcome barriers in rare cancers and enable discoveries.
To protect patient confidentiality, the study data set is de-identified before it is shared, which includes the masking of patient IDs and the reclassification of unique patient-reported demographic responses. The resulting clinically annotated genomic data set of the ASCproject is shared publicly on cBioPortal on an ongoing and regular basis as the data are generated.
The authors acknowledged the ASCproject advocacy partners: Angiosarcoma Awareness, The Paula Takacs Foundation for Sarcoma Research, Sarcoma Alliance for Research through Collaboration, Sarcoma Alliance, Sarcoma Foundation of America, The Sarcoma Coalition, and Target Cancer Foundation. They are especially thankful to all members of the Count Me In team. This research was supported by anonymous philanthropic support to the Broad Institute.
Reference
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; Published online 10 February 2020. https://doi.org/10.1038/s41591-019-074