An Accessible Communication System for Population-Based Genetic Testing: Development and Usability Study.

BACKGROUND: Genetic testing uptake is low, despite the well-established connection between pathogenic variants in certain cancer-linked susceptibility genes and ovarian cancer risk. Given that most major insurers cover genetic testing for those with a family history suggestive of hereditary cancer, the issue may lie in access to genetic testing. Remotely accessible web-based communication systems may improve awareness, and uptake, of genetic testing services. OBJECTIVE: This study aims to present the development and formative evaluation of the multistep web-based communication system required to support the implementation of, and access to, genetic testing. METHODS: While designing the multistep web-based communication system, we considered various barriers and facilitators to genetic testing, guided by dimensions of accessibility. In addition to conducting usability testing, we performed ongoing assessments focusing on the function of the web-based system and participant response rates, with the goal of continuing to make modifications to the web-based communication system as it is in use. RESULTS: The combined approach of usability testing and expert user experience consultation resulted in several modifications to the multistep web-based communication system, including changes that related to imagery and content, web accessibility, and general organization of the web-based system. All recommendations were made with the goal of improving the overall accessibility of the web-based communication system. CONCLUSIONS: A multistep web-based communication system appears to be an effective way to address many potential barriers to access, which may otherwise make genetic testing difficult for at-risk individuals to participate in. Importantly, some dimensions of access were easy to assess before study recruitment, but other aspects of the communication system required ongoing assessment during the implementation process of the Making Genetic Testing Accessible study.

Bridging the Gap: A Priorities Assessment Tool to Support Shared Decision Making, Maximize Appointment Time, and Increase Patient Satisfaction in Women With Ovarian Cancer.

PURPOSE: Women with ovarian cancer identify patient-physician communication as an essential element in determining treatment course and believe a discussion about goals and values should precede treatment decisions. We sought to develop a patient-centered priorities assessment tool for women with ovarian cancer that could streamline communication, enhance treatment discussions, and increase patient satisfaction. MATERIALS AND METHODS: We designed a priorities assessment tool using a validated ovarian cancer symptom index (National Comprehensive Cancer Center-Functional Assessment of Cancer Therapy Ovarian Symptom Index-18) combined with an index to assess daily quality-of-life priorities. The tool was distributed to women with ovarian cancer in small focus group settings and online, followed by a postactivity feedback form. RESULTS: In this pilot study, 36 women completed the priorities assessment tool and 35 completed the postactivity feedback form between September 2015 and May 2016. All participants reported that the tool was easy to understand and comprehensive in scope. Twenty-nine participants (82.9%) completed the tool in 10 minutes or less. Most participants (n = 31, 86.1%) were able to stratify their priorities and identify 5 top treatment-related priorities. Participants who indicated that their goals and priorities had changed since diagnosis (n = 25, 69.4%) reported that the tool helped to identify current goals and priorities (22 [88%] of 25 participants) and would help them feel more comfortable participating in shared decision making with their medical team (21 [84%] of 25 participants). CONCLUSION: A patient-centered priorities assessment tool was easy to complete and viewed as comprehensive and useful in a pilot cohort of women with ovarian cancer. Use of a priorities assessment tool has the potential to enhance communication, promote shared decision making, and improve patient satisfaction.

Multigene panels in Ashkenazi Jewish patients yield high rates of actionable mutations in multiple non-BRCA cancer-associated genes.

OBJECTIVE: To evaluate the results of multigene panel testing among Ashkenazi Jewish compared with non-Ashkenazi Jewish patients. METHODS: We reviewed the medical records for all patients who underwent multigene panel testing and targeted BRCA1/2 testing at a single institution between 6/2013-1/2015. Clinical actionability for identified pathogenic mutations was characterized based on the National Comprehensive Cancer Network (NCCN) guidelines and consensus statements and expert opinion for genes not addressed by these guidelines. RESULTS: Four hundred and fifty-four patients underwent multigene panel screening, including 138 Ashkenazi Jewish patients. The median patient age was fifty-two years. Three hundred and fifty-four patients (78%) had a personal history of cancer. Two hundred and fifty-one patients had breast cancer, 49, ovarian cancer, 26, uterine cancer and 20, colorectal cancer. We identified 62 mutations in 56 patients and 291 variants of uncertain significance in 196 patients. Among the 56 patients with mutations, 51 (91%) had actionable mutations. Twenty mutations were identified by multigene panels among Ashkenazi Jewish patients, 18 of which were in genes other than BRCA1/2. A review of targeted BRCA1/2 testing performed over the same study period included 103 patients and identified six mutations in BRCA1/2, all of which occurred in Ashkenazi Jewish patients. Among all Ashkenazi Jewish patients undergoing genetic testing, 25/183 (14%) had a mutation, 24/25 of which were actionable (96%) and 17/25 patients (68%) had mutations in non BRCA1/2 genes. CONCLUSIONS: With the rapid acceptance of multigene panels there is a pressing need to understand how this testing will affect patient management. While traditionally many Ashkenazi Jewish patients have undergone targeted BRCA1/2 testing, our data suggest consideration of multigene panels in this population as the majority of the results are clinically actionable and often in genes other than BRCA1/2.

A pharmacokinetic evaluation of topotecan as a cervical cancer therapy.

INTRODUCTION: Topotecan was initially approved for the treatment of recurrent ovarian cancer. In cervical cancer, it has been investigated for its potential as part of systemic therapy for advanced and/or recurrent disease and in combination with cisplatin and radiation as a first-line treatment for advanced disease. As a topoisomerase I (topo I) inhibitor, its activity is predicted to be schedule-dependent and potentiated in a schedule-dependent manner by its interaction with DNA damaging agents. AREAS COVERED: The cytotoxicity of topotecan is believed to be due to double-stranded DNA damage produced when the DNA replication 'fork' on the opposing DNA strand is interrupted by the ternary complex formed by topotecan, topoisomerase I and DNA. This review focuses on: i) combination studies of cisplatin + topotecan both as neoadjuvant and with concomitant radiation; ii) adding this drug as a radiosensitizer in pilot studies for locally advanced disease and iii) topotecan as part of non-cisplatin combinations in metastatic disease. EXPERT OPINION: Cervical cancer continues to claim many victims among parts of the world where early detection and/or vaccination programs are not systemically applied. Topotecan is an attractive building block for improving therapy against advanced disease.

Replication-selective herpes simplex virus type 1 mutant therapy of cervical cancer is enhanced by low-dose radiation.

Herpes simplex virus type 1 (HSV-1)-based oncolytic treatment is a promising therapeutic approach for malignancy. Recombinant strains of HSV-1 containing mutations in the ICP 34.5 protein have been shown to replicate preferentially in rapidly proliferating malignant cells, resulting in a direct cytolytic effect. We assessed the efficacy of multimutated HSV-1 strains on human cervical cancer, and then used these viruses in combination with radiation therapy, the standard treatment for cervical cancer. The HSV-1 mutants 4009, 7020, 3616, and G207 induced significant lysis of three established human cervical cancer cell lines in vitro in a dose-dependent manner. G207 intratumoral treatment of established subcutaneous C33a tumors in severe combined immunodeficient (SCID) mice significantly reduced tumor burden by 50%. Weekly and triweekly treatments improved efficacy and inhibited flank tumor growth in an administration frequency-dependent manner without toxicity. Combination therapy of a low dose of radiation (1.5 or 3 Gy) and replication-selective HSV mutants infection exhibited increased antitumor effects against cervical cancer cells in vitro. The in vivo effect of G207 combined with low-dose radiation was studied in Me180 xenografts in athymic mice. Treatment of established Me180 tumor nodules with 3 Gy followed by intratumoral G207 administration greatly improved efficacy, resulting in 42% complete eradication of tumor. In conclusion, single and multiple intratumoral injections of G207 significantly reduced tumor burden in xenogeneic models of cervical cancer, and the addition of low-dose radiation further potentiated the effect. These results suggest that replication-selective HSV-1 mutants may be potent oncolytic agents for the treatment of cervical cancer.