Gebra Cuyun Carter

Broadening recommendations for hereditary cancer testing have increased demand for genetics services and prompted alternatives to referral-based pretest genetic counseling. This systematic review summarized testing models used by nongenetics providers in point-of-care settings and associated clinical outcomes. PubMed and Embase were searched from January 2014 to March 2024. Outcomes included testing uptake, treatment decisions, turnaround time, posttest counseling, and cascade testing. Forty-eight articles reporting 46 studies were included; 41 involved patients with cancer, and 5 included patients with and without cancer. Pretest education methods included provider-mediated conversations, video, digital platforms, and written materials. Testing uptake ranged from 49% to 100% in patients with cancer and 18% to 87% in mixed populations meeting testing criteria. Among studies with comparison groups, 19 of 20 observed similar or higher testing uptake, and 10 of 11 noted numerically shorter turnaround times with point-of-care testing. Fourteen studies reported test-informed management. Posttest counseling and cascade testing were inconsistently reported. Overall, the diverse studies demonstrated pathways for timely access to testing, often associated with increased uptake and impacts on clinical management; however, most focused on breast, ovarian, or prostate cancer populations in academically affiliated clinics. Further research should evaluate posttest services and equitable implementation in broader settings.

In the US, breast cancer is the most common female cancer. Personalized treatment strategies, informed by genomic assays and germline genetic testing (GGT), can optimize therapeutic decisions and improve patient outcomes along the hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer treatment pathway. To evaluate the cost-effectiveness of combining molecular tools, including the 21-gene assay, GGT, and comprehensive genomic profiling (CGP) when compared to no testing, to inform the treatment of patients with HR+/HER2- breast cancer from the US societal perspective. A health economic model was developed which stratified patients with node-negative (N0) and node-positive (1-3 positive nodes) (N1) early-stage breast cancer according to the 21-gene assay and GGT. Long-term outcomes were simulated using a Markov model. CGP was used to stratify patients who progressed to advanced disease for actionable genomic alterations. Clinical inputs and costs were sourced from published literature. A clinician survey was used for inputs to reflect current US clinical practice. Over a lifetime horizon, the full testing strategy was dominant (more effective and cost-saving) in N0 patients and cost-effective in N1 (ICER = $54,734/QALY) patients. The model estimated quality-adjusted life year (QALY) gains of 0.322 and cost savings of $7,168 for N0 patients and 0.130 QALYs gain and additional costs of $7,109 for N1 patients. Sensitivity analyses supported the robustness of the analysis. Compared to no testing, the full testing strategy of genetic and genomic testing was more effective at a lower cost or was cost-effective, supporting the goal to increase the survival and the quality-of-life of women with breast cancer along the cancer care continuum.

Background The Oncotype DX Breast Recurrence Score^® test is prognostic for distant recurrence in hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2-) early-stage breast cancer. It is the only multigene assay able to predict chemotherapy benefit, validated by evidence from randomized controlled trials. Using a Japanese public healthcare payer perspective, a cost-effectiveness analysis was conducted comparing the Oncotype DX^® test to clinico-pathological risk assessment in women with node-negative (N0), HR+/HER2- early breast cancer. Methods A decision-tree stratified patients according to their Recurrence Score^® (RS^®) result and adjuvant chemotherapy allocation. A Markov model was used to capture lifetime costs and outcomes of the chosen treatment. Distributions of clinical risk in N0 patients were derived from the TAILORx trial. Distant recurrence probability conditional on RS result was calculated using TAILORx and NSABP-20 studies. Endocrine and chemoendocrine therapy selection was informed by a Clinical Expert Survey and the literature. Drugs and medical device costs were obtained from the Ministry of Health, Labour and Welfare. Results The Oncotype DX test was dominant (i.e. cost-saving and more effective) as it generated more quality-adjusted life-years (QALYs) (0.207) at a lower cost (-¥649,596) compared to clinico-pathological risk assessment in the overall population. Cost savings were primarily driven by a lower incidence of distant recurrence (-¥1,007,177). The Oncotype DX test was dominant in all subgroups except for one, which was cost-effective. Conclusions Use of the Oncotype DX test to guide treatment decisions improves patient outcomes while reducing healthcare costs for N0 HR+/HER2- early-stage breast cancer in Japan.

This study sought to design predictive machine learning models to assign stage at diagnosis to colorectal cancer patients using only administrative claims

PURPOSE: With an increase in approved targeted therapies for non–small cell lung cancer (NSCLC), tumor profiling that maximizes identification of patients eligible for these treatments is essential. In this study, we compare testing approaches for newly diagnosed advanced or metastatic NSCLC. METHODS: An economic model was developed to estimate the annual costs and clinical outcomes associated with testing alternatives. Patients were assigned alterations on the basis of rates observed in published literature. Treatment approaches included no genomic testing; sequential single-gene testing; or a whole-exome, whole-transcriptome (WES/WTS) comprehensive genomic profiling to inform use of targeted therapies. The budget impact and survival implications of WES/WTS were compared head to head with the other testing approaches, and uncertainty was assessed in sensitivity analyses. In scenario analyses, tests that incorporate both DNA and RNA were compared with tests using DNA sequencing alone when assuming the prevalence of fusions that can only be identified by RNA ranged from 2.5% to 14%. RESULTS: Compared with no testing, WES/WTS reduced costs by $8,809 in US dollars (USD) per patient tested while increasing median overall survival by an average of 3.9 months. When compared with sequential single-gene testing, use of WES/WTS decreased costs by $14,602 (USD) per patient and had a minimal survival benefit. A test that included both RNA and DNA sequencing reduced costs by $400-$1,724 (USD) and increased identification of actionable alterations by 2.3%-13.0% across the range of fusion prevalence. CONCLUSION: Use of WES/WTS improved clinical outcomes while reducing costs. These findings should be considered when choosing between tumor profiling approaches.

Background and Objectives: The 21-gene assay (the Oncotype DX Breast Recurrence Score^® test) estimates the 10-year risk of distant recurrence in hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer to inform adjuvant chemotherapy decisions. The cost-effectiveness of the 21-gene assay compared against standard clinical-pathological risk tools alone for HR+/HER2- early-stage breast cancer was assessed using an economic model informed by evidence from randomized controlled trials. Materials and Methods: A cost-effectiveness model consisted of a decision-tree to stratify patients according to their Recurrence Score (RS) results and the use of adjuvant chemotherapy, followed by a Markov component to estimate the long-term costs and outcomes of the chosen treatment. Distributions of patients and distant recurrence probabilities were derived from the TAILORx (N0) and RxPONDER (N1) trials. The model was evaluated from a healthcare payer and societal perspective. Endocrine therapy and chemotherapy use were informed using clinical expert opinion to reflect US clinical practice and were combined with Medicare drug costs (2021) to estimate the cost of treatment. Societal costs included lost productivity and patient out-of-pocket costs obtained from literature. Results: The Oncotype DX test generated more quality-adjusted life-years (QALYs) (N0: 0.25; N1: 0.08) at a lower cost (N0: -$13,395; N1: -$2526) compared to clinical-pathological risk alone from a societal cost perspective. The overall conclusions from the model did not change when considering a payer perspective. The main cost drivers were avoidance of distant recurrence for N0 (-$12,578), and the cost of adjuvant chemotherapy for N1 (-$2133). Lost productivity had a major impact in the societal perspective analysis (N0: -$4607; N1: -$1586). Conclusion: Adjuvant chemotherapy decisions based on the RS result led to more life year gains and lower healthcare costs (dominant) compared to using clinical-pathological risk factors alone among patients with HR+/HER2- N0 and N1 early-stage breast cancer.

Aims: The availability of targeted therapies for oncology patients is increasing. Available genomic tests to identify treatment-eligible patients include single gene tests and gene panel tests, including the whole-exome, whole-transcriptome OncoExTra^TM test. We assessed the costs and clinical benefits of test choice. Methods: A Microsoft Excel-based model was developed to evaluate test choice in patients with advanced/metastatic non-small cell lung cancer (NSCLC), breast, prostate, and colorectal cancer. Treatment pathways were based on NCCN guidelines and medical expert opinion. Inputs were derived from published literature. Annual economic results and lifetime clinical results with OncoExTra testing were projected per-tested-patient and compared with single gene testing and no testing. Separately, results were estimated for a US health plan without the OncoExTra test and with its use in 5% of patients. Results: Compared with no genomic testing, OncoExTra test use increased costs by $4,915 per patient; however, 82%-92% of individuals across tumor types were identified as eligible for targeted therapy or a clinical trial. Compared with single gene testing, OncoExTra test use decreased costs by $9,966 per-patient-tested while increasing use of approved or investigational targeted therapies by 20%. When considering a hypothetical health plan with 1 million members, 858 patients were eligible for genomic testing. Using the OncoExTra test in 5% of those eligible, per-member per-month costs decreased by $0.003, ranging from cost-savings of $0.026 in NSCLC patients to a $0.009 increase in prostate cancer patients. Cost-savings were driven by reduced treatment costs with increased clinical trial enrollment and reduced direct and indirect medical costs associated with targeted treatments. Conclusions: Limitations include the required simplifications in modeling complex conditions that may not fully reflect evolving real-world testing and treatment patterns. Compared to single-gene testing, results indicate that using NGS test such as OncoExTra identified more actionable alterations, leading to improved outcomes and reduced costs.

Liquid biopsies—tests that detect circulating tumor cellular components in the bloodstream—have the potential to transform cancer by reducing health inequities in screening, diagnostics, and monitoring. Today, liquid biopsies are being used to guide treatment choices for patients and monitor for cancer recurrence, and promising work in multi-cancer early detection is ongoing. However, without awareness of the barriers to adoption of this new technology and a willingness to build mitigation efforts into the implementation of widespread liquid biopsy testing, the communities that could most benefit may be the last to access and use them. In this work, we review the challenges likely to affect the accessibility of liquid biopsies in both the general population and underserved populations, and recommend specific actions to facilitate equitable access for all patients.