Operational Ontology for Oncology (O3): A Professional Society-Based, Multistakeholder, Consensus-Driven Informatics Standard Supporting Clinical and Research Use of Real-World Data From Patients Treated for Cancer

PURPOSE: The ongoing lack of data standardization severely undermines the potential for automated learning from the vast amount of information routinely archived in electronic health records (EHRs), radiation oncology information systems, treatment planning systems, and other cancer care and outcomes databases. We sought to create a standardized ontology for clinical data, social determinants of health, and other radiation oncology concepts and interrelationships. METHODS AND MATERIALS: The American Association of Physicists in Medicine\u27s Big Data Science Committee was initiated in July 2019 to explore common ground from the stakeholders\u27 collective experience of issues that typically compromise the formation of large inter- and intra-institutional databases from EHRs. The Big Data Science Committee adopted an iterative, cyclical approach to engaging stakeholders beyond its membership to optimize the integration of diverse perspectives from the community. RESULTS: We developed the Operational Ontology for Oncology (O3), which identified 42 key elements, 359 attributes, 144 value sets, and 155 relationships ranked in relative importance of clinical significance, likelihood of availability in EHRs, and the ability to modify routine clinical processes to permit aggregation. Recommendations are provided for best use and development of the O3 to 4 constituencies: device manufacturers, centers of clinical care, researchers, and professional societies. CONCLUSIONS: O3 is designed to extend and interoperate with existing global infrastructure and data science standards. The implementation of these recommendations will lower the barriers for aggregation of information that could be used to create large, representative, findable, accessible, interoperable, and reusable data sets to support the scientific objectives of grant programs. The construction of comprehensive real-world data sets and application of advanced analytical techniques, including artificial intelligence, holds the potential to revolutionize patient management and improve outcomes by leveraging increased access to information derived from larger, more representative data sets

Cyclooxygenase-2 and other targets of adjuvant therapies for uveal melanoma

Uveal melanoma has a high mortality rate, with approximately 45% of patients dying due to liver metastasis within 15 years of initial diagnosis and local treatment. As the eye lacks lymphatics, there is no staging of uveal melanoma according to lymph node metastasis. The search for new prognostic factors and therapeutic targets is therefore crucial to the advancement of uveal melanoma research. The expression of cyclooxygenase-2 (COX-2) has been investigated in human malignancies such as cutaneous melanoma. Immunohistochemical studies were therefore used to show that uveal melanomas do express COX-2 and that this expression is associated with various histopathological markers of poor prognosis. A novel sub-classification of mixed-cell-type tumours was devised, according to COX-2 expression.The numerous studies of COX-2 expression in human malignancies have focused on COX-2 expression in tumour cells. This work shows COX-2 to be expressed in uveal melanoma tumour cells and tumour-associated macrophages (TAM), with a higher amount of COX-2 expression associated with a higher amount of TAM infiltration. These results may help explain the poor prognosis previously attributed to a high amount of TAM infiltration in uveal melanoma.This thesis also investigated the co-expression of COX-2, insulin-like growth factor 1 receptor (IGF-IR) and phosphorylated-Akt (p-Akt). A recent paper had shown IGF-1R expression to be associated with a higher risk of uveat melanoma metastasis. IGF-1R expression, present to different degrees in almost all uveal melanoma cases, represents the presence of the receptor, whereas p-Akt expression represents an activated downstream pathway. This thesis showed that p-Akt is expressed in uveal melanoma. While some uveal melanoma cases co-expressed COX-2, IGF-1R and p-Akt, all cases were positive for at least one of the three markers.Studies in human malignancies, including uveal melanoma, have shown COX-2 inhibitors to have effects on both COX-2 positive and negative tumour cells. The effects of COX-2 inhibitors on IGF-1R and p-Akt have been postulated as possible mechanisms behind these COX-2 independent effects. This work has provided a rationale for the study of COX-2 inhibitors, alone or in combination with IGF-1R inhibitors, as systemic adjuvant treatment of this life-threatening intra-ocular malignancy

Production of NO by macrophages exposed to conditioned medium from COX-2 transfected cell lines with and without the addition of amfenac

<p><b>Copyright information:</b></p><p>Taken from "The effects of a cyclooxygenase-2 (COX-2) expression and inhibition on human uveal melanoma cell proliferation and macrophage nitric oxide production"</p><p>http://www.carcinogenesis.com/content/6/1/17</p><p>Journal of Carcinogenesis 2007;6():17-17.</p><p>Published online 27 Nov 2007</p><p>PMCID:PMC2222223.</p><p></p

Production of NO by macrophages exposed to melanoma conditioned medium with and without the addition of amfenac

<p><b>Copyright information:</b></p><p>Taken from "The effects of a cyclooxygenase-2 (COX-2) expression and inhibition on human uveal melanoma cell proliferation and macrophage nitric oxide production"</p><p>http://www.carcinogenesis.com/content/6/1/17</p><p>Journal of Carcinogenesis 2007;6():17-17.</p><p>Published online 27 Nov 2007</p><p>PMCID:PMC2222223.</p><p></p

Graph of proliferation rates of four human uveal melanoma cell lines (92

<p><b>Copyright information:</b></p><p>Taken from "The effects of a cyclooxygenase-2 (COX-2) expression and inhibition on human uveal melanoma cell proliferation and macrophage nitric oxide production"</p><p>http://www.carcinogenesis.com/content/6/1/17</p><p>Journal of Carcinogenesis 2007;6():17-17.</p><p>Published online 27 Nov 2007</p><p>PMCID:PMC2222223.</p><p></p>1, MKT-BR, OCM-1, SP6.5) and the UW-1 transformed melanocytic cell line, with and without addition of amfenac. RPMI alone was used as a control