No abstract

Guidelines currently state that genetic testing is clinically indicated for all individuals diagnosed with ovarian cancer. Individuals with a prior diagnosis of ovarian cancer who have not received genetic testing represent missed opportunities to identify individuals with inherited high-risk cancer variants. For deceased individuals, post-mortem genetic testing of pathology specimens allows surviving family members to receive important genetic risk information. The Genetic Risk Assessment in Ovarian Cancer (GRACE) study aims to address this significant healthcare gap using a “traceback testing” approach to identify individuals with a prior diagnosis of ovarian cancer and offer genetic risk information to them and their family members. This study will assess the potential ethical and privacy concerns related to an ovarian cancer traceback testing approach in the context of patients who are deceased, followed by implementation and evaluation of the feasibility of an ovarian cancer traceback testing approach using tumor registries and archived pathology tissue. Descriptive and statistical analyses will assess health system and patient characteristics associated with the availability of pathology tissue and compare the ability to contact and uptake of genetic testing between patients who are living and deceased. The results of this study will inform the implementation of future traceback programs.

Current guidelines state that genetic testing is clinically indicated for all individuals diagnosed with ovarian cancer. Individuals with a prior diagnosis of ovarian cancer who have not received genetic testing represent missed opportunities to identify individuals with inherited high risk cancer variants. The Genetic Risk Assessment in Ovarian Cancer (GRACE) study aims to address this significant healthcare gap using a “traceback testing” approach to identify individuals with a prior diagnosis of ovarian cancer and offer genetic risk information to them and their family members. Tumor registry data at two integrated health care systems (Kaiser Permanente Northwest and Kaiser Permanente Colorado) was used to identify individuals diagnosed with ovarian cancer from 2008 to 2019 who either did not receive genetic testing or had genetic testing limited to BRCA1 and BRCA2 and could benefit from more recent testing and testing using a comprehensive panel of cancer risk genes. Of the 180 eligible individuals contacted for participation, 51 have enrolled and consented to testing, reflecting an uptake rate of 28%. Of the 34 participants with genetic testing results, 7 (21%) have been found to carry a pathogenic or likely pathogenic variant in a cancer risk gene. The study genetic counselor supported these participants in sharing their genetic test results with at-risk relatives to facilitate cascade testing. Of the 20 at-risk relatives eligible for cascade testing, 10 have undergone genetic testing (50% cascade testing uptake) of which 4 have been found to carry the familial variant. Overall, these findings indicate the promise of such traceback testing approaches in providing potentially life-saving information to individuals and their family members at increased genetic risk for cancer who may otherwise be missed. Future efforts of the GRACE study will focus on the feasibility of leveraging archived pathology tissue to provide genetic risk information to family members of individuals with a diagnosis of ovarian cancer who are deceased. The GRACE study can inform broad implementation of future traceback programs across health care systems, providing life-saving information to prevent and mitigate the burden of ovarian and other hereditary cancers. Citation Format: Heather S. Feigelson, Yolanda K. Prado, Tia Kauffman, Ana A. Reyes, Jamilyn M. Zepp, Mahesh Maiyani, Jennifer Sawyer, Larissa L. White, S. Bianca Salas, Sarah Vertrees, Alan F. Rope, Sheila Weinmann, Nora B. Henrikson, Sandra S. Lee, Jessica E. Hunter. Feasibility of a traceback approach to facilitate genetic testing in the Genetic Risk Analysis in Ovarian Cancer (GRACE) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1447.

Background Although an association between dementia and certain infectious diseases, such as HIV, has been well‐established, recent publications have also concerningly hinted at the possibility of its association with a much more common infectious disease, as well: herpes simplex virus (HSV). We sought to better investigate potential associations between HSV diagnosis and treatment with incident dementia in a large, retrospective cohort. Method We conducted our analysis among members of Kaiser Permanente Northwest aged 50 and older between 2000‐2019. We matched individuals with an HSV diagnosis during this time frame to three individuals, each, without HSV, based on age at index date (HSV diagnosis date for cases and a reference date for controls), sex, and membership length prior to index date. Follow‐up time started at the index date and ended on the date of dementia diagnosis, membership end date, death, or end of follow‐up, whichever came first. We defined HSV and dementia diagnoses by ICD‐9/‐10 codes recorded in the electronic health record. We defined herpes simplex antiviral treatment, based on in‐network pharmacy fills. We used survival analysis to examine the associations between dementia with HSV diagnosis (yes/no, overall, by sex, age, and HSV type) and HSV medication fills (yes/no; and by tertiles of medication dispensed). We adjusted models by demographic and clinical factors. Result 87,432 persons (21,661 with HSV) were included. The mean age was 60.9 years and 69% were female. Over a mean follow‐up of 6.1 years, 4,507 developed dementia. HSV diagnoses – overall and Type 2 – was significantly associated with lower risk of dementia (Figure). Anti‐viral medication (any versus none) was not associated with dementia, and we did not see a dose response when examining dose by tertile (Figure). Conclusion In contrast to the recent reports, we found a slight, but statistically‐significant association between HSV diagnosis with dementia. We did not observe a lower risk of dementia associated with anti‐herpetic treatment, also as had been previously reported. The relationship between HSV and dementia may be complex and deserves further study. However, that we did not see a positive association between HSV and dementia in our study is very encouraging.

Objective Tumor registries in integrated healthcare systems (IHCS) have high precision for identifying incident cancer but often miss recently diagnosed cancers or those diagnosed outside of the IHCS. We developed an algorithm using the electronic medical record (EMR) to identify people with a history of cancer not captured in the tumor registry to identify adults, aged 40–65 years, with no history of cancer. Materials and Methods The algorithm was developed at Kaiser Permanente Colorado, and then applied to 7 other IHCS. We included tumor registry data, diagnosis and procedure codes, chemotherapy files, oncology encounters, and revenue data to develop the algorithm. Each IHCS adapted the algorithm to their EMR data and calculated sensitivity and specificity to evaluate the algorithm’s performance after iterative chart review. Results We included data from over 1.26 million eligible people across 8 IHCS; 55 601 (4.4%) were in a tumor registry, and 44848 (3.5%) had a reported cancer not captured in a registry. The common attributes of the final algorithm at each site were diagnosis and procedure codes. The sensitivity of the algorithm at each IHCS was 90.65%–100%, and the specificity was 87.91%–100%. Discussion Relying only on tumor registry data would miss nearly half of the identified cancers. Our algorithm was robust and required only minor modifications to adapt to other EMR systems. Conclusion This algorithm can identify cancer cases regardless of when the diagnosis occurred and may be useful for a variety of research applications or quality improvement projects around cancer care.