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PURPOSE: To develop an electronic health record (EHR)–based clinical decision support (CDS) tool to promote guideline-recommended cancer risk management among patients with Lynch syndrome (LS), an inherited cancer syndrome that confers an increased risk of colorectal and other cancer types. MATERIALS AND METHODS: We conducted a cross-sectional study to determine the baseline prevalence and predictors of guideline-recommended colonic surveillance and annual genetics program visits among patients with LS. Multivariable log-binomial regressions estimated prevalence ratios (PRs) of cancer risk management adherence by baseline sociodemographic and clinical characteristics. These analyses provided rationale for the development of an EHR-based CDS tool to support patients and clinicians with LS-related endoscopic surveillance and annual genetics program visits. The CDS leverages an EHR platform linking discrete genetic data to LS Genomic Indicators, in turn driving downstream clinician- and patient-facing CDS. RESULTS: Among 323 patients with LS, cross-sectional adherence to colonic surveillance and annual genetics program visits was 69.3% and 55.4%, respectively. Patients with recent electronic patient portal use were more likely to be adherent to colonic surveillance (PR, 1.67; 95% CI, 1.11 to 2.52). Patients more recently diagnosed with LS were more likely to be adherent to annual genetics program visits (PR, 0.58; 95% CI, 0.44 to 0.76 for 2-4 years; PR, 0.62; 95% CI, 0.51 to 0.75 for ≥4 compared with <2 years). Our EHR-based CDS tool is now active for 421 patients with LS throughout our health system. CONCLUSION: We have successfully developed an EHR-based CDS tool to promote guideline-recommended cancer risk management among patients with LS. Development of a novel electronic health record–based clinical decision support tool for patients with Lynch syndrome. [ABSTRACT FROM AUTHOR]

Background: Timely targeted treatment initiation can be challenging because additional biomarker testing is needed for eligibility. The authors hypothesized that timely targeted treatment improves survival relative to nontimely initiation in metastatic HER2+ gastroesophageal adenocarcinoma (GEA). Methods: The authors performed a retrospective cohort study of metastatic HER2+ GEA treated with first‐line (1L) systemic therapy from January 2011 to December 2017 using a nationwide electronic health record–derived deidentified database. Timely targeted treatment—trastuzumab initiation within 14 days after starting 1L chemotherapy—was assessed as a time‐varying exposure. Nontimely targeted treatment included patients who initiated trastuzumab after 14 days or who lacked documentation of receiving trastuzumab. Extended Cox regressions compared overall survival (OS) and progression‐free survival (PFS) between timely and nontimely groups. Results: A total of 320 patients were included; 59.1% received timely trastuzumab. Relative to nontimely initiation, timely trastuzumab was associated with significantly higher OS (2‐year OS, 32.1% vs 15.3%; adjusted hazard ratio [HR], 0.67; 95% CI, 0.51‐0.88) and PFS (2‐year PFS, 9.2% vs 3.7%; adjusted HR, 0.71; 95% CI, 0.55‐0.93). Results remained similar in sensitivity analyses 1) using alternative "timeliness" definitions up to 70 days after starting 1L chemotherapy, 2) comparing any trastuzumab, regardless of timing of initiation, to no trastuzumab, and 3) excluding patients lacking documentation of receiving trastuzumab. Conclusions: Improved survival was observed among metastatic HER2+ GEA patients treated with trastuzumab versus those who were not, regardless of timing of initiation. Although these results reassure clinicians that modest targeted treatment delays may not be detrimental to outcomes, efforts should still ensure that all metastatic HER2+ GEA patients receive trastuzumab. Time‐to‐treatment initiation is an important quality metric in oncology, but there is a paucity of data on the impact of timely targeted treatment for which additional biomarker testing is needed to identify eligible patients. In this study of patients with metastatic HER2‐overexpressing gastroesophageal adenocarcinoma, overall and progression‐free survival rates were higher for patients treated with trastuzumab compared to those who were not, regardless of the timing of initiation. [ABSTRACT FROM AUTHOR]

Background: Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice. Methods: We conducted a qualitative study of oncology clinicians to identify barriers to using preemptive PGx testing to guide chemotherapy dosing in patients with gastrointestinal malignancies. Each participant completed a semi-structured interview informed by the Consolidated Framework for Implementation Research (CFIR). Interviews were analyzed using an inductive content analysis approach. Results: Participants included sixteen medical oncologists and nine oncology pharmacists from one academic medical center and two community hospitals in Pennsylvania. Barriers to the use of preemptive PGx testing to guide chemotherapy dosing mapped to four CFIR domains: intervention characteristics, outer setting, inner setting, and characteristics of individuals. The most prominent themes included 1) a limited evidence base, 2) a cumbersome and lengthy testing process, and 3) a lack of insurance coverage for preemptive PGx testing. Additional barriers included clinician lack of knowledge, difficulty remembering to order PGx testing for eligible patients, challenges with PGx test interpretation, a questionable impact of preemptive PGx testing on clinical care, and a lack of alternative therapeutic options for some patients found to have actionable PGx variants. Conclusions: Successful adoption of preemptive PGx-guided chemotherapy dosing in patients with gastrointestinal malignancies will require a multifaceted effort to demonstrate clinical effectiveness while addressing the contextual factors identified in this study. [ABSTRACT FROM AUTHOR]

BACKGROUND: Anti human epidermal growth factor receptor 2 (anti‐HER2) therapy with trastuzumab improves overall survival in patients with advanced, HER2‐positive gastroesophageal adenocarcinoma (GEA) and is now incorporated into national guidelines. However, little is known about adherence to and determinants of timely HER2 testing and trastuzumab initiation in routine practice. METHODS: The authors performed a cross‐sectional study of patients who had advanced GEA diagnosed between January 2011 and June 2019 in a nationwide electronic health record‐derived database. The annual prevalences of both timely HER2 testing (defined within 21 days after advanced diagnosis) and timely trastuzumab initiation (defined within 14 days after a positive HER2 result) were calculated. Log‐binomial regressions estimated adjusted prevalence ratios comparing timely HER2 testing and trastuzumab initiation by patient and tumor characteristics. RESULTS: In total, the cohort included 6032 patients with advanced GEA of whom 1007 were HER2‐positive. Between 2011 and 2019, timely HER2 testing increased from 22.4% to 44.5%, whereas timely trastuzumab initiation remained stable at 16.3%. No appreciable differences in timely testing or trastuzumab initiation were noted by age, sex, race, or insurance status. Compared with patients who had metastatic disease at diagnosis, patients who had early stage GEA who did not undergo surgery were less likely to receive timely HER2 testing and trastuzumab initiation (testing prevalence ratio, 0.69; 95% CI, 0.64‐0.75; treatment prevalence ratio, 0.32; 95% CI, 0.18‐0.56), as were patients with early stage disease who subsequently developed a distant recurrence (testing prevalence ratio, 0.56; 95% CI, 0.47‐0.65; treatment prevalence ratio, 0.61; 95% CI, 0.24‐1.55). CONCLUSIONS: In patients with advanced GEA, guideline‐recommended HER2 testing and anti‐HER2 therapy remain underused. Uptake may improve with universal HER2 testing regardless of stage. Timely HER2 biomarker testing and targeted therapy administration remain in use for patients with advanced gastroesophageal adenocarcinoma. Compared with patients initially diagnosed with de novo metastatic disease, those diagnosed with early stage disease who develop a recurrence or who do not undergo curative surgery are less likely to receive timely precision oncology care. [ABSTRACT FROM AUTHOR]

The rapid advancement of precision oncology, the use of molecular and genetic testing to tailor cancer therapies to individual patients, has uniquely positioned the field of oncology to move beyond race-based medicine. Embedding clinical decision support systems into the EHR has been shown to facilitate decision making in other areas of cancer diagnosis, treatment, and supportive care,[53] and it has been associated with decreased racial disparities in the management of nononcologic conditions such as hypertension.[39] This approach should also be leveraged to standardize precision oncology care for all patients, regardless of race. These types of patient communications informed by the principles of behavioral economics may empower and nudge patients to initiate conversations with their providers about genetic testing, targeted therapy, or participation in precision oncology research. [Extracted from the article]

The rapid advancement of precision oncology, the use of molecular and genetic testing to tailor cancer therapies to individual patients, has uniquely positioned the field of oncology to move beyond race-based medicine. Embedding clinical decision support systems into the EHR has been shown to facilitate decision making in other areas of cancer diagnosis, treatment, and supportive care,[53] and it has been associated with decreased racial disparities in the management of nononcologic conditions such as hypertension.[39] This approach should also be leveraged to standardize precision oncology care for all patients, regardless of race. These types of patient communications informed by the principles of behavioral economics may empower and nudge patients to initiate conversations with their providers about genetic testing, targeted therapy, or participation in precision oncology research. [Extracted from the article]

Gastrointestinal (GI) malignancies are among the most commonly diagnosed cancers worldwide. Despite the introduction of targeted and immunotherapy agents in the treatment landscape, cytotoxic agents, such as fluoropyrimidines and irinotecan, remain as the cornerstone of chemotherapy for many of these tumors. Pharmacogenetics (PGx) is a rapidly evolving field that accounts for interpatient variability in drug metabolism to predict therapeutic response and toxicity. Given the significant incidence of severe treatment‐related adverse events associated with cytotoxic agents, utilizing PGx can allow clinicians to better anticipate drug tolerability while minimizing treatment interruptions or delays. In this review, the PGx profiles of drug‐gene pairs with potential impact in GI malignancy therapy – DPYD‐5‐fluorouracil/capecitabine and UGT1A1‐irinotecan – and the available clinical evidence of their roles in reducing severe adverse events are discussed. Considerations for clinical implementation, such as optimal laboratory workflows, electronic health record integration, and stakeholder engagement, as well as provider education, are addressed. Last, exploratory PGx markers in GI malignancy treatment are described. As the PGx knowledge base rapidly evolves, pharmacists will be vital in leveraging their pharmacology knowledge and clinical skills to implement PGx testing in the clinic. [ABSTRACT FROM AUTHOR]

Background: Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice.Methods: We conducted a qualitative study of oncology clinicians to identify barriers to using preemptive PGx testing to guide chemotherapy dosing in patients with gastrointestinal malignancies. Each participant completed a semi-structured interview informed by the Consolidated Framework for Implementation Research (CFIR). Interviews were analyzed using an inductive content analysis approach.Results: Participants included sixteen medical oncologists and nine oncology pharmacists from one academic medical center and two community hospitals in Pennsylvania. Barriers to the use of preemptive PGx testing to guide chemotherapy dosing mapped to four CFIR domains: intervention characteristics, outer setting, inner setting, and characteristics of individuals. The most prominent themes included 1) a limited evidence base, 2) a cumbersome and lengthy testing process, and 3) a lack of insurance coverage for preemptive PGx testing. Additional barriers included clinician lack of knowledge, difficulty remembering to order PGx testing for eligible patients, challenges with PGx test interpretation, a questionable impact of preemptive PGx testing on clinical care, and a lack of alternative therapeutic options for some patients found to have actionable PGx variants.Conclusions: Successful adoption of preemptive PGx-guided chemotherapy dosing in patients with gastrointestinal malignancies will require a multifaceted effort to demonstrate clinical effectiveness while addressing the contextual factors identified in this study. [ABSTRACT FROM AUTHOR]