Model-Based Re-Examination of the Effectiveness of Tumor/Immunohistochemistry and Direct-to-Sequencing Protocols for Lynch Syndrome Case Finding in Endometrial Cancer

2021 ◽  
pp. OP.20.00988
Author(s):  
James M. Gudgeon ◽  
Michael W. Varner ◽  
Jing Hao ◽  
Marc S. Williams
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Simulation Models ◽  
Clinical Effectiveness ◽  
Case Finding ◽  
Current Evidence ◽  
Screening Programs ◽  
Direct Testing ◽  
Variable Success ◽  
Potential Impact

PURPOSE: Despite widespread provision of Lynch syndrome (LS) screening programs, questions remain about the most effective and efficient protocol for LS case finding. The purpose of this study was to explore the performance of the two protocols widely shown to be the most efficient and effective, respectively: immunohistochemical (IHC) staining of tumor and direct-to-sequencing (DtS) in endometrial cancer populations. METHODS: Simulation models were developed to explore performance of the IHC and DtS protocols, updated to reflect current evidence. Analyses explicitly account for protocol complexity and failure points, as well as decreased sequencing costs. Key outcomes are percent of LS cases identified, total protocol costs and efficiency, and break-even analyses of sequencing costs. All costs are in 2020 US dollars (USD). RESULTS: Under plausible conditions, the IHC protocol is expected to identify 40%-78% of LS cases and DtS protocol from 49% to 97%. When the key variable success in proceeding to sequencing is fixed for both protocols at 50%, 75%, and 100%, the DtS protocol is 9%, 12%, and 16% better at case finding, respectively, than the IHC protocol. The break-even cost of sequencing is about $488 USD when the outcome is total direct testing protocol costs; it is about $670 USD when the outcome is cost per LS case detected. CONCLUSION: This study quantifies the plausible differences in the clinical effectiveness and cost-effectiveness of the two LS case-finding protocols. We demonstrate the large influence of success in proceeding to sequencing and potential impact of decreasing sequencing prices.

scholarly journals Clinical and Cost Effectiveness of Two “New” Lynch Syndrome Case Finding Protocols in Endometrial Cancer Population Contrasted with the IHC-based Protocol

2019 ◽  
Author(s):  
James M. Gudgeon ◽  
Michael W. Varner ◽  
Mia Hashibe ◽  
Marc S. Williams
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Screening Program ◽  
Cost Effective ◽  
Case Finding ◽  
Local Data ◽  
Screening Programs ◽  
Family History Questionnaire ◽  
Program Costs ◽  
Index Cases

AbstractPurposeTo investigate the effectiveness and costs of two Lynch syndrome screening protocols among endometrial cancer (EC) patients and compare to an immunohistochemistry (IHC)–based protocol.MethodsAnalytic models were developed to represent the two protocols: a brief cancer family history questionnaire (bFHQ) and direct-to-sequencing of the germline. Data from reviews of published literature, augmented by local data and expert opinion were used to populate the model representing the number of women diagnosed in the U.S. in 2018. Multiple analyses employing simulation modeling were performed to estimate a variety of clinical and economic outcomes.ResultsUnder conditions considered here to be plausible, the bFHQ is expected to miss 58% (min./max. = 24 to 80%) of LS index cases, a direct-to-sequencing protocol to miss 30% (min./max. = 6% to 53%), and the IHC-based protocol based on previous analysis 58% (min./max. = 33 to 80%). When direct costs of testing and genetic counseling are added to the models, the total screening program costs for the bFHQ protocol are substantially lower at all sequencing price points than the other protocols. For example, at the low end of the sequencing price point (ie, $250), the total cost of screening programs for IHC, bFHQ, and sequencing are $22.9 million, $5.3 million, and $13.8 million, respectively. The best estimate of the break-even price of sequencing, when the cost of the program is equivalent between the IHC and sequencing protocols, is about $635.ConclusionThe bFHQ and direct-to-sequencing LS screening protocols are more effective and cost effective at identifying LS index cases than the standard IHC-based protocol under the conditions represented in our models. These estimates of various outcome metrics of the three LS index case finding protocols may help stakeholders make decisions of the use of limited healthcare dollars.

Lynch syndrome-related non-endometrioid endometrial cancer: analysis of outcomes

2019 ◽  
Vol 30 (1) ◽  
pp. 56-61
Author(s):  
Giorgio Bogani ◽  
Maria Grazia Tibiletti ◽  
Maria Teresa Ricci ◽  
Ileana Carnevali ◽  
Viola Liberale ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Disease Free Survival ◽  
Oncologic Outcomes ◽  
Cox Models ◽  
Matching Algorithm ◽  
Pathogenic Variants ◽  
Propensity Matching ◽  
Endometrioid Endometrial Cancer

ObjectiveWomen with Lynch syndrome have a risk up to 40–60% of developing endometrial cancer, which is higher than their risk of developing colorectal or ovarian cancer. To date, no data on the outcomes of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer are available. The goal of this study was to evaluate the outcome of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer.MethodsData from consecutive patients diagnosed with Lynch syndrome and with a histological diagnosis of non-endometrioid endometrial cancer were retrospectively collected in two referral institutes in Italy. A case–control comparison (applying a propensity matching algorithm) was performed in order to compare patients with proven Lynch syndrome and controls. Inclusion criteria were: (a) histologically-proven endometrial cancer; (b) detection of a germline pathogenic variant in one of the MMR genes; (c) adequate follow-up. Only carriers of pathogenic or likely pathogenic variants (ie, class 5 and 4 according to the InSiGHT classification) were included in the study. Survival outcomes were assessed using KaplanMeier and Cox models.ResultsOverall, 137 patients with Lynch syndrome were collected. Mean patient age was 49.2 (10.9) years. Genes involved in the Lynch syndrome included MLH1, MSH2, and MSH6 in 43%, 39%, and 18% of cases, respectively. The study population included 27 patients with non-endometrioid endometrial cancer, who were matched 1:2 with patients with sporadic cancers using a propensity matching algorithm. After a median follow-up of 134 months (range 1–295), 2 (7.4%) of the 27 patients developed recurrent disease (3 and 36 months) and subsequently died of disease (7 and 91 months). Patients diagnosed with Lynch syndrome experienced better disease-free survival (HR 7.86 (95% CI 1.79 to 34.5); p=0.006) and overall survival (HR 5.33 (95% CI 1.18 to 23.9); p=0.029) than controls.ConclusionsNon-endometrioid endometrial cancer occurring in patients with Lynch syndrome might be associated with improved oncologic outcomes compared with controls. Genetic/molecular profiling should be investigated in order to better understand the mechanism underlying the prognosis.

scholarly journals Prospective Study of Combined Colon and Endometrial Cancer Screening in Women With Lynch Syndrome: A Patient-Centered Approach

2011 ◽  
Vol 7 (1) ◽  
pp. 43-47 ◽  
Author(s):  
Marilyn Huang ◽  
Charlotte Sun ◽  
Stephanie Boyd-Rogers ◽  
Jennifer Burzawa ◽  
Andrea Milbourne ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Screening ◽  
Lynch Syndrome ◽  
Prospective Study ◽  
Patient Centered

Combined colon and endometrial cancer screening is a patient-centered approach that is feasible and acceptable and may improve adherence to Lynch syndrome screening recommendations.

scholarly journals Current Evidence and Future Perspectives on the Effective Practice of Patient-Centered Laboratory Medicine

2015 ◽  
Vol 61 (4) ◽  
pp. 589-599 ◽  
Author(s):  
Mike J Hallworth ◽  
Paul L Epner ◽  
Christoph Ebert ◽  
Corinne R Fantz ◽  
Sherry A Faye ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Clinical Effectiveness ◽  
Laboratory Medicine ◽  
Current Evidence ◽  
Patient Centered ◽  
Definition Of ◽  
Current Utilization ◽  
Measures Of Effectiveness ◽  
The Impact ◽  
Primary Measure

AbstractBACKGROUNDSystematic evidence of the contribution made by laboratory medicine to patient outcomes and the overall process of healthcare is difficult to find. An understanding of the value of laboratory medicine, how it can be determined, and the various factors that influence it is vital to ensuring that the service is provided and used optimally.CONTENTThis review summarizes existing evidence supporting the impact of laboratory medicine in healthcare and indicates the gaps in our understanding. It also identifies deficiencies in current utilization, suggests potential solutions, and offers a vision of a future in which laboratory medicine is used optimally to support patient care.SUMMARYTo maximize the value of laboratory medicine, work is required in 5 areas: (a) improved utilization of existing and new tests; (b) definition of new roles for laboratory professionals that are focused on optimizing patient outcomes by adding value at all points of the diagnostic brain-to-brain cycle; (c) development of standardized protocols for prospective patient-centered studies of biomarker clinical effectiveness or extraanalytical process effectiveness; (d) benchmarking of existing and new tests in specified situations with commonly accepted measures of effectiveness; (e) agreed definition and validation of effectiveness measures and use of checklists for articles submitted for publication. Progress in these areas is essential if we are to demonstrate and enhance the value of laboratory medicine and prevent valuable information being lost in meaningless data. This requires effective collaboration with clinicians, and a determination to accept patient outcome and patient experience as the primary measure of laboratory effectiveness.

Adoption of universal next generation sequencing for lynch syndrome screening in endometrial cancer

2022 ◽  
Vol 164 (1) ◽  
pp. 4-5
Author(s):  
Isabel Rodriguez ◽  
Sarah Strickland ◽  
David Wells ◽  
Enna Manhardt ◽  
Eric Konnick ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Next Generation Sequencing ◽  
Lynch Syndrome ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals N-Acetylcysteine for the Treatment of Psychiatric Disorders: A Review of Current Evidence

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Soo Liang Ooi ◽  
Ruth Green ◽  
Sok Cheon Pak
Keyword(s):  
Mood Disorders ◽  
Adjunctive Therapy ◽  
Negative Symptoms ◽  
Clinical Effectiveness ◽  
Good Evidence ◽  
Current Evidence ◽  
Chronic Obstructive ◽  
Obsessive Compulsive ◽  
Brain Functions ◽  
Psychiatric Conditions

N-acetylcysteine, a sulphur-containing amino acid for the treatment of paracetamol overdose and chronic obstructive pulmonary disease, is a widely available off-the-shelf oral antioxidant supplement in many countries. With the potential to modulate several neurological pathways, including glutamate dysregulation, oxidative stress, and inflammation that can be beneficial to the brain functions, N-acetylcysteine is being explored as an adjunctive therapy for many psychiatric conditions. This narrative review synthesises and presents the current evidence from systematic reviews, meta-analyses, and latest clinical trials on N-acetylcysteine for addiction and substance abuse, schizophrenia, obsessive-compulsive and related disorders, and mood disorders. Good evidence exists to support the use of N-acetylcysteine as an adjunct treatment to reduce the total and negative symptoms of schizophrenia. N-acetylcysteine also appears to be effective in reducing craving in substance use disorders, especially for the treatment of cocaine and cannabis use among young people, in addition to preventing relapse in already abstinent individuals. Effects of N-acetylcysteine on obsessive-compulsive and related disorders, as well as on mood disorders, remain unclear with mixed reviews, even though promising evidence does exist. Larger and better-designed studies are required to further investigate the clinical effectiveness of N-acetylcysteine in these areas. Oral N-acetylcysteine is safe and well tolerated without any considerable adverse effects. Current evidence supports its use as an adjunctive therapy clinically for psychiatric conditions, administered concomitantly with existing medications, with a recommended dosage between 2000 and 2400 mg/day.

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