Germline Genetic Testing After Cancer Diagnosis.

Importance: Germline genetic testing is recommended by practice guidelines for patients diagnosed with cancer to enable genetically targeted treatment and identify relatives who may benefit from personalized cancer screening and prevention. Objective: To describe the prevalence of germline genetic testing among patients diagnosed with cancer in California and Georgia between 2013 and 2019. Design, Setting, and Participants: Observational study including patients aged 20 years or older who had been diagnosed with any type of cancer between January 1, 2013, and March 31, 2019, that was reported to statewide Surveillance, Epidemiology, and End Results registries in California and Georgia. These patients were linked to genetic testing results from 4 laboratories that performed most germline testing for California and Georgia. Main Outcomes and Measures: The primary outcome was germline genetic testing within 2 years of a cancer diagnosis. Testing trends were analyzed with logistic regression modeling. The results of sequencing each gene, including variants associated with increased cancer risk (pathogenic results) and variants whose cancer risk association was unknown (uncertain results), were evaluated. The genes were categorized according to their primary cancer association, including breast or ovarian, gastrointestinal, and other, and whether practice guidelines recommended germline testing. Results: Among 1 369 602 patients diagnosed with cancer between 2013 and 2019 in California and Georgia, 93 052 (6.8%) underwent germline testing through March 31, 2021. The proportion of patients tested varied by cancer type: male breast (50%), ovarian (38.6%), female breast (26%), multiple (7.5%), endometrial (6.4%), pancreatic (5.6%), colorectal (5.6%), prostate (1.1%), and lung (0.3%). In a logistic regression model, compared with the 31% (95% CI, 30%-31%) of non-Hispanic White patients with male breast cancer, female breast cancer, or ovarian cancer who underwent testing, patients of other races and ethnicities underwent testing less often: 22% (95% CI, 21%-22%) of Asian patients, 25% (95% CI, 24%-25%) of Black patients, and 23% (95% CI, 23%-23%) of Hispanic patients (P < .001 using the χ2 test). Of all pathogenic results, 67.5% to 94.9% of variants were identified in genes for which practice guidelines recommend testing and 68.3% to 83.8% of variants were identified in genes associated with the diagnosed cancer type. Conclusions and Relevance: Among patients diagnosed with cancer in California and Georgia between 2013 and 2019, only 6.8% underwent germline genetic testing. Compared with non-Hispanic White patients, rates of testing were lower among Asian, Black, and Hispanic patients.

Cascade Genetic Risk Education and Testing in Families With Hereditary Cancer Syndromes: A Pilot Study.

PURPOSE: Cascade genetic risk evaluation in families with hereditary cancer can reduce the burden of disease but the rate of germline genetic testing in relatives of patients at risk is low. METHODS: We identified all 277 women diagnosed with breast cancer in Georgia in 2017 who linked to a clinically actionable germline pathogenic variant through a Surveillance, Epidemiology, and End Results registry-variant linkage initiative. We surveyed them, and then invited eligible respondents to an online platform hosted by a navigator that offered cancer genetic risk education and germline genetic testing to untested relatives. We randomly assigned patient-family clusters at the time of the patient enrollment offer to free versus $50 (USD) test cost. Patients invited relatives to join the study through personalized e-mail. Enrolled relatives received online cancer genetic education and the opportunity to order clinical germline genetic testing through the platform. The primary outcome was the number of relatives who ordered genetic testing. RESULTS: One hundred twenty-five of 277 patients completed surveys (45.2%). Most respondents were eligible for the trial offer (113 of 125; 90.4%). In the free testing arm, 20 of 56 eligible patients participated (35.7% of eligible respondents) and they invited 28 relatives: 12 relatives enrolled and 10 ordered testing. In the $50 (USD) arm, 16 of 57 eligible patients participated (28.1%) and they invited 38 relatives: 18 relatives enrolled and 17 ordered testing. CONCLUSION: Cascade genetic testing in families with hereditary cancer syndromes accrued through a population-based cancer registry can be achieved through an online platform that offers genetic risk education and low-cost testing to relatives. A modest charge did not appear to influence the percentage of participating patients, numbers of participating relatives, and numbers of relatives who received genetic testing.

Development and psychometric properties of a brief measure of subjective decision quality for breast cancer treatment.

BACKGROUND: Breast cancer patients face several preference-sensitive treatment decisions. Feelings such as regret or having had inadequate information about these decisions can significantly alter patient perceptions of recovery and recurrence. Numerous objective measures of decision quality (e.g., knowledge assessments, values concordance measures) have been developed; there are far fewer measures of subjective decision quality and little consensus regarding how the construct should be assessed. The current study explores the psychometric properties of a new subjective quality decision measure for breast cancer treatment that could be used for other preference sensitive decisions. METHODS: 320 women aged 20-79 diagnosed with AJCC stage 0 - III breast cancer were surveyed at two cancer specialty centers. Decision quality was assessed with single items representing six dimensions: regret, satisfaction, and fit as well as perceived adequacy of information, time, and involvement. Women rated decision quality for their overall treatment experience and surgery, chemotherapy, and radiation decisions separately. Principle components was used to explore factor structure. After scales were formed, internal consistency was computed using Cronbach's alpha. The association of each of the four final scales with patient characteristics scores was examined by Pearson correlation. RESULTS: For overall breast cancer treatment as well as surgery, chemotherapy, and radiation decisions, the six items yielded a single factor solution. Factor loadings of the six decision items were all above .45 across the overall and treatment-specific scales, with the exception of "Right for You" for chemotherapy and radiation. Internal consistency was 0.77, 0.85, 0.82, and 0.78 for the overall, surgery, chemotherapy, and radiation decision quality scales, respectively. CONCLUSIONS: Our measure of subjective appraisal of breast cancer treatment decisions includes 5 related elements; regret and satisfaction as well as perceived adequacy of information, time, and involvement. Future research is needed to establish norms for the measure as is further psychometric testing, particularly to examine how it is associated with outcomes such as quality of life, psychological coping and objective decision quality.

Hospital readmissions among patients with decompensated cirrhosis.

OBJECTIVES: Early rehospitalizations have been well characterized in many disease states, but not among patients with cirrhosis. The aims of this study were to identify the frequency, costs, predictors, and preventable causes of hospital readmissions among patients with decompensated cirrhosis. METHODS: Rates of readmission were calculated for 402 patients discharged after one of the following complications of cirrhosis: ascites, spontaneous bacterial peritonitis, renal failure, hepatic encephalopathy, or variceal hemorrhage. Costs of readmissions were calculated using the hospital accounting system. Predictors of time to first readmission were determined using Cox regression, and predictors of hospitalization rate/person-years were determined using negative binomial regression. The independent association between readmission rate and mortality was determined using Cox regression. Admissions within 30 days of discharge were assessed by two reviewers to determine if preventable. RESULTS: Overall, 276 (69%) subjects had at least one nonelective readmission, with a median time to first readmission of 67 days. By 1 week after discharge, 14% of subjects had been readmitted, and 37% were readmitted within 1 month. The mean costs for readmissions within 1 week and between weeks 1 and 4 were $28,898 and $20,581, respectively. During a median follow-up of 203 days, the median number of readmissions was 2 (range 0-40), with an overall rate of 3 hospitalizations/person-years. Patients with more frequent readmissions had higher risk of subsequent mortality, despite adjustment for confounders including the Model for End-stage Liver Disease (MELD) score. Predictors of time to first readmission included MELD score, serum sodium, and number of medications on discharge; predictors of hospitalization rate included these variables as well as the number of cirrhosis complications and being on the transplant list at discharge. Among 165 readmissions within 30 days, 22% were possibly preventable. CONCLUSIONS: Hospital readmissions among patients with decompensated cirrhosis are common, costly, moderately predictable, in some cases, possibly preventable, and independently associated with mortality. These findings support the development of disease management interventions to prevent rehospitalization.

Patient decision making about organ quality in liver transplantation.

It is challenging to discuss the use of high-risk organs with patients, in part because of the lack of information about how patients view this topic. This study was designed to determine how patients think about organ quality and to test formats for risk communication. Semistructured interviews of 10 patients on the waiting list revealed limited understanding about the spectrum of organ quality and a reluctance to consider anything but the best organs. A computerized quantitative survey was then conducted with an interactive graph to elicit the risk of graft failure that patients would accept. Fifty-eight percent of the 95 wait-listed patients who completed the survey would accept only organs with a risk of graft failure of 25% or less at 3 years, whereas 18% would accept only organs with the lowest risk possible (19% at 3 years). Risk tolerance was increased when the organ quality was presented relative to average organs rather than the best organs and when feedback was provided about the implications for organ availability. More than three-quarters of the patients reported that they wanted an equal or dominant role in organ acceptance decisions. Men tended to prefer lower risk organs (mean acceptable risk = 29%) in comparison with women (mean acceptable risk = 35%, P = 0.04), but risk tolerance was not associated with other demographic or clinical characteristics (eg, the severity of liver disease). In summary, patients want to be involved in decisions about organ quality. Patients' risk tolerance varies widely, and their acceptance of high-risk organs can be facilitated if we present the risks of graft failure with respect to average organs and provide feedback about the implications for organ availability.

Public health impact of antiviral therapy for hepatitis C in the United States.

UNLABELLED: Despite dramatic improvements in antiviral therapy for hepatitis C, there is reason to believe that the uptake of antiviral therapy remains limited. The aims of this study were to determine the number of patients being treated with antiviral therapy in the U.S., to estimate the public health impact of these treatment patterns, and to identify barriers to treatment for patients with hepatitis C. Data on the number of new patient pegylated interferon prescriptions each year, from 2002-2007, was obtained from Wolters Kluwer Inc., which maintains an electronic audit of pharmacies nationwide. A Markov model was created of the population with chronic hepatitis C in the U.S. from 2002 to 2030, and was used to estimate the number of liver-related deaths caused by hepatitis C that will be prevented by current treatment patterns. The National Health and Nutrition Evaluation Survey (NHANES) Hepatitis C Follow-Up Questionnaire was used to investigate reasons for lack of treatment and to identify strategies for improving access. Approximately 663,000 patients received antiviral therapy between 2002 and 2007, and treatment rates appear to be declining. If this trend continues, only 14.5% of liver-related deaths caused by hepatitis C from 2002-2030 will be prevented by antiviral therapy. Results from the NHANES questionnaire suggest that the primary barrier to treatment is lack of diagnosis, with 69/133 (adjusted proportion 49%) of respondents previously unaware that they had hepatitis C. CONCLUSION: Efforts to improve rates of diagnosis and treatment will be required if the future public health burden of hepatitis C is to be ameliorated.