Real-World Impact of an In-House Dihydropyrimidine Dehydrogenase (DPYD) Genotype Test on Fluoropyrimidine Dosing, Toxicities, and Hospitalizations at a Multisite Cancer Center.

PURPOSE: Fluoropyrimidine-related toxicity and mortality risk increases significantly in patients carrying certain DPYD genetic variants with standard dosing. We implemented DPYD genotyping at a multisite cancer center and evaluated its impact on dosing, toxicity, and hospitalization. METHODS: In this prospective observational study, patients receiving (reactive) or planning to receive (pretreatment) fluoropyrimidine-based chemotherapy were genotyped for five DPYD variants as standard practice per provider discretion. The primary end point was the proportion of variant carriers receiving fluoropyrimidine modifications. Secondary end points included mean relative dose intensity, fluoropyrimidine-related grade 3+ toxicities, and hospitalizations. Fisher's exact test compared toxicity and hospitalization rates between pretreatment carriers, reactive carriers, and wild-type patients. Univariable and multivariable logistic regression identified factors associated with toxicity and hospitalization risk. Kaplan-Meier methods estimated time to event of first grade 3+ toxicity and hospitalization. RESULTS: Of the 757 patients who received DPYD genotyping (median age 63, 54% male, 74% White, 19% Black, 88% GI malignancy), 45 (5.9%) were heterozygous carriers. Fluoropyrimidine was modified in 93% of carriers who started treatment. In 442 patients with 3-month follow-up, 64%, 31%, and 30% of reactive carriers, pretreatment carriers, and wild-type patients had grade 3+ toxicity, respectively (P = .085); 64%, 25%, and 13% were hospitalized (P < .001). Reactive carriers had 10-fold higher odds of hospitalization compared with wild-type patients (P = .001), whereas no significant difference was noted between pretreatment carriers and wild-type patients. Time-to-event of toxicity and hospitalization were significantly different between genotype groups (P < .001), with reactive carriers having the earliest onset and highest incidence. CONCLUSION: DPYD genotyping prompted fluoropyrimidine modifications in most carriers. Pretreatment testing reduced toxicities and hospitalizations compared with reactive testing, thus normalizing the risk to that of wild-type patients, and should be considered standard practice.

Addressing barriers to increased adoption of DPYD genotyping at a large multisite cancer center.

PURPOSE: To describe the implementation of an in-house genotyping program to detect genetic variants linked to impaired dihydropyrimidine dehydrogenase (DPD) metabolism at a large multisite cancer center, including barriers to implementation and mechanisms to overcome barriers to facilitate test adoption. SUMMARY: Fluoropyrimidines, including fluorouracil and capecitabine, are commonly used chemotherapy agents in the treatment of solid tumors, such as gastrointestinal cancers. DPD is encoded by the DPYD gene, and individuals classified as DPYD intermediate and poor metabolizers due to certain genetic variations in DPYD can experience reduced fluoropyrimidine clearance and an increased risk of fluoropyrimidine-related adverse events. Although pharmacogenomic guidelines provide evidence-based recommendations for DPYD genotype-guided dosing, testing has not been widely adopted in the United States for numerous reasons, including limited education/awareness of clinical utility, lack of testing recommendations by oncology professional organizations, testing cost, lack of accessibility to a comprehensive in-house test and service, and prolonged test turnaround time. Based on stakeholder feedback regarding barriers to testing, we developed an in-house DPYD test and workflow to facilitate testing in multiple clinic locations at Levine Cancer Institute. Across 2 gastrointestinal oncology clinics from March 2020 through June 2022, 137 patients were genotyped, and 13 (9.5%) of those patients were heterozygous for a variant and identified as DPYD intermediate metabolizers. CONCLUSION: Implementation of DPYD genotyping at a multisite cancer center was feasible due to operationalization of workflows to overcome traditional barriers to testing and engagement from all stakeholders, including physicians, pharmacists, nurses, and laboratory personnel. Future directions to scale and sustain testing in all patients receiving a fluoropyrimidine across all Levine Cancer Institute locations include electronic medical record integration (eg, interruptive alerts), establishment of a billing infrastructure, and further refinement of workflows to improve the rate of pretreatment testing.

A review of R-DHAP administration in the outpatient setting and a case of the alternative regimen R-DHAX given outpatient for refractory diffuse large B-cell lymphoma.

INTRODUCTION: Several regimens for treating hematologic malignancies are given inpatient due to multiple factors. Many clinicians are evaluating methods to deliver traditionally inpatient regimens in the outpatient setting to increase patient satisfaction, improve access to therapy, and reduce costs. A regimen traditionally administered inpatient, dexamethasone, cytarabine, and cisplatin (DHAP) is a common and effective salvage regimen for relapsed/refractory non-Hodgkin's lymphoma. DHAX, which substitutes oxaliplatin for cisplatin, has been identified as a reasonable alternative to DHAP and offers the potential for tolerable administration in the outpatient setting as well. CASE DESCRIPTION: A 74-year-old patient with double hit relapsed/refractory diffuse large B cell lymphoma was given rituximab, dexamethasone, high-dose cytarabine, and oxaliplatin (R-DHAX) in our outpatient clinic; however, this regimen is traditionally administered in the inpatient setting. Our main obstacle being cytarabine doses traditionally given 12 h apart. The outpatient regimen given to our patient was rituximab and oxaliplatin on day 1, cytarabine dose one late afternoon on day 2, cytarabine dose two early morning on day 3, and dexamethasone on days 1-4. Doses of oxaliplatin and cytarabine were reduced due to thrombocytopenia experienced with Cycle 1. He did not experience any increased toxicities or complications associated with the regimen moving forward. DISCUSSION: This illustrates a unique administration of R-DHAX in an infusion center that operates during typical outpatient clinic hours. Both DHAP and DHAX, with or without rituximab, administered in the outpatient setting may be options to consider in relapsed/refractory non-Hodgkin's lymphoma.

Use of board games, historical calendars, and trading cards in a history of psychology class.

This article describes three activities for students created for a history of psychology course: various board games, trading cards, and calendars. Data are provided on their effectiveness. Suggestions for incorporating the activities are described.