Despite collectively accounting for 25% of tumors in U.S. adults, rare cancers have significant unmet clinical needs as they are difficult to study due to low incidence and geographically dispersed patient populations. We sought to assess whether a patientpartnered research approach using online engagement can overcome these challenges and accelerate scientific discovery in rare cancers, focusing on angiosarcoma (AS), an exceedingly rare sarcoma with a dismal prognosis and an annual U.S. incidence of 300 cases. Here, we describe the development of the Angiosarcoma Project (ASCproject), an initiative enabling patients across the U.S. and Canada to remotely share their clinical information and biospecimens for research. The project generates and publicly releases clinically annotated genomic data on tumor and germline specimens on an ongoing basis. Over 18 months, 338 AS patients registered for the ASCproject, comprising a significant fraction of all patients. Whole exome sequencing of 47 AS tumors revealed several recurrently mutated genes, including KDR, TP53, and PIK3CA. Activating mutations in PIK3CA were observed nearly exclusively in primary breast AS, suggesting a therapeutic rationale in these patients. AS of the head, neck, face, and scalp (HNFS) was associated with high tumor mutation burden and a dominant mutational signature of UV light exposure, suggesting that UV damage may be a causative factor in HNFS AS and that this AS subset might be amenable to immune checkpoint inhibitor therapy. Medical record review revealed two patients with HNFS AS received off-label treatment with anti-PD-1 therapy and experienced exceptional responses, highlighting immune checkpoint inhibition as a therapeutic avenue for HNFS AS. This patient-partnered approach has catalyzed an opportunity to discover the etiology and potential therapies for AS patients. Collectively, this proof of concept study demonstrates that empowering patients to directly participate in research can overcome barriers in rare diseases and enable biological and clinical discoveries.

Despite collectively accounting for 25% of tumors in U.S. adults, rare cancers have significant unmet clinical needs as they are difficult to study due to low incidence and geographically dispersed patient populations. We sought to assess whether a patientpartnered research approach using online engagement can overcome these challenges and accelerate scientific discovery in rare cancers, focusing on angiosarcoma (AS), an exceedingly rare sarcoma with a dismal prognosis and an annual U.S. incidence of 300 cases. Here, we describe the development of the Angiosarcoma Project (ASCproject), an initiative enabling patients across the U.S. and Canada to remotely share their clinical information and biospecimens for research. The project generates and publicly releases clinically annotated genomic data on tumor and germline specimens on an ongoing basis. Over 18 months, 338 AS patients registered for the ASCproject, comprising a significant fraction of all patients. Whole exome sequencing of 47 AS tumors revealed several recurrently mutated genes, including KDR, TP53, and PIK3CA. Activating mutations in PIK3CA were observed nearly exclusively in primary breast AS, suggesting a therapeutic rationale in these patients. AS of the head, neck, face, and scalp (HNFS) was associated with high tumor mutation burden and a dominant mutational signature of UV light exposure, suggesting that UV damage may be a causative factor in HNFS AS and that this AS subset might be amenable to immune checkpoint inhibitor therapy. Medical record review revealed two patients with HNFS AS received off-label treatment with anti-PD-1 therapy and experienced exceptional responses, highlighting immune checkpoint inhibition as a therapeutic avenue for HNFS AS. This patient-partnered approach has catalyzed an opportunity to discover the etiology and potential therapies for AS patients. Collectively, this proof of concept study demonstrates that empowering patients to directly participate in research can overcome barriers in rare diseases and enable biological and clinical discoveries.

1076 Background: The Metastatic Breast Cancer Project is a nationwide research study, launched in Oct 2015 in collaboration with patients (pts) and advocacy groups, that directly engages pts through social media and seeks to empower them to share their experiences, clinical information, and samples to accelerate research. Methods: MBC pts enroll by providing their information at mbcproject.org. Pts are sent a saliva kit and asked to mail back a sample which is used to extract germline DNA. We contact pts medical providers and obtain medical records (MRs) and stored tumor samples. Pts may also submit a blood sample, used to extract cell free DNA (cfDNA). Whole exome sequencing (WES) is performed on tumor, germline, and cfDNA; transcriptome sequencing is performed on tumor. Clinical and genomic data are used to generate genomic landscapes in pt subgroups and to identify mechanisms of response and resistance to therapies. Data are shared widely through public databases. Pts receive regular study updates. Results: In 12 months, 2908 MBC pts from 50 states enrolled. 95% completed the 16-question survey about their cancer, treatments, and demographics. 1730 (60%) completed the online consent form. 100-200 pts continue to enroll monthly. To date, 1539 saliva kits were mailed and 1120 samples were received (73%). 992 unique treating institutions were reported by pts, including 733 institutions reported by only 1 pt each and 5 institutions reported by more than 40 pts each. We have obtained MRs from 253 patients (67% yield) and tumor samples from 85 pts (67% yield). WES was successfully completed for 79 tumors of 88 attempted (90%). WES has been performed on initial cfDNA samples. Conclusions: A direct-to-patient approach enabled rapid identification of thousands of MBC pts willing to share MRs, saliva, and tumor samples, including many with rare phenotypes. Remote acquisition of MRs, saliva, tumor, and blood for pts located throughout the US is feasible. We estimate that for ~33% of consenting patients, we can obtain medical records, saliva, and tumor tissue. Genomic analysis of tumor and cfDNA from subgroups including young pts, pts with extraordinary responses, and pts with de novo MBC will be presented.

No abstract

Universal application of hydrophilic hydrogels like poly(hydroxy ethyl methacrylate) [p(HEMA)], as biomaterials is limited due to their inabil ity to favorably affect eukaryotic cell growth. In an attempt to favorably manipulate surface properties, a series of HEMA copolymers was made with 10-40% aminoethyl methacrylamide (AEMA), aminopropyl methacrylamide (APMA), Quadrol methacrylate (QM), N,N'-bis(2-hydroxypropyl)aminoethyl meth acrylamide (HPAEMA) or dimethylaminoethyl methacrylate (DMAEMA). Balb/c 3T3 fibroblast cell growth was observed on HEMA:AEMA (80:20), HEMA:QM (80:20) and HEMA:HPAEMA (90:10) copolymers. Cell growth on HEMA: AEMA (80:20) was comparable to HEMA:DMAEMA (60:40). HEMA copolymers containing APMA, a homolog of AEMA, exhibited cytotoxicity. Cationic groups of primary and tertiary amines present in the HEMA copoly mer hydrogels favorably contribute to the support of cell growth. The effect of hydroxyl groups on cell growth appears to be favorable. The extent of cell growth varied with the concentration of the cationic groups in the hydrogel. The cytotoxicity of the HEMA:APMA copolymers as compared with the bio compatibility of the HEMA:AEMA copolymers suggests that the length of the branch from the polymer chain for copolymers with primary amino groups may be a critical factor in biocompatibility.