Abstract P2-12-12: MyNauseaRisk assay - Predicting chemotherapy-induced delayed nausea using a blood-based assay
Authors: Nicole F Laslett, Dillon D McCourt, Kinjal Parikh, John F Kennedy, Zonera A Ali, Erik L Zeger, Aarti L Shevade, Tracey L Evans, Paul B Gilman, Margaretha Wallon
Journal: Cancer Research (2020)

Abstract BACKGROUND: Nausea and vomiting are some of the most common and distressing side effects of chemotherapy according to patients. Chemotherapy-induced nausea and vomiting (CINV) places a substantial burden on patients and their loved ones, which greatly reduces the quality of life, nutritional habits, ability to work and socialize, and adhere to treatment regimens. Therefore, assessment of CINV is an essential component of care for patients receiving chemotherapy. Multiple factors influence the incidence of CINV with the chemotherapy regimen, both type and dosage, being the primary risk factor. It is generally assumed that the strongest patient-related factors are younger age and female sex. However, reports in the literature have demonstrated that using these factors clinicians underestimate the prevalence of CINV, especially delayed nausea. Thus, there is a need for risk assessment tools to accurately identify patients requiring anti-emetic regimens to improve quality of life of patients and their families. Our assay is based on the knowledge that chemotherapeutic agents cause bursts of reactive oxygen species (ROS) resulting in cellular damage and release of substances that activate receptors in the chemoreceptor trigger zone. Glutathione (GSH), a key antioxidant, is responsible for maintaining redox homeostasis by neutralizing ROS. Therefore, we hypothesized that a patient’s risk of CINV may reflect individual variations in the efficiency to scavenge and neutralize ROS after chemotherapy. METHODS: Patients enrolled in our institutional review board approved study (N= 220), were treated in the adjuvant or neoadjuvant setting with highly or moderately emetogenic chemotherapies for their breast cancer diagnosis. Blood samples were drawn from chemotherapy naïve patients and used in the predictive blood assay. The assay is based on the conversion of a bioactive probe, hydroxyethyl disulfide, into mercaptoethanol, which once normalized to red blood cell count, indicates glutathione recycling capacity. Incidence and severity of delayed nausea symptoms were collected from notes in medical records as well as anti-emetic prescription history. RESULTS: A recent second evaluation of patients treated with platinum-based therapies confirmed our previously published data, demonstrating a correlation between low glutathione recycling capacity and risk of delayed nausea for patients with lung and colon cancer (N=111; misclassification rate 0.153; AUC 0.72). In this study, we evaluated age-matched patients treated with anthracycline/cyclophosphamide (AC)(N=42), docetaxel/cyclophosphamide (TC)(N=39), docetaxel/carboplatin/trastuzumab (TCH)(N=27) or docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP)(N=25). The incidence of moderate-to-severe nausea was highest in the AC (38.1%) and TCHP (36.0%) groups. The TCH group had the lowest incidence of patients (11%) reporting delayed nausea. SAS/STAT v.14.1 classification trees demonstrated a weak association between anthracycline-induced delayed nausea and MyNauseaRisk score (misclassification rate 0.333; AUC 0.67). Similarly, patients treated with TC demonstrated a correlation between MyNauseaRisk score and severity of nausea as previously seen for platinum therapies. The algorithm determined that age stratification of patients in the TCHP group prior to applying the MyNauseaRisk score reduced the misclassification rate (0.280) and improved the AUC (0.72). CONCLUSION: The results from this exploratory prospective study suggests that a reduced ability to recycle GSH in the blood may offer an objective prediction of delayed nausea, possibly allowing for optimal anti-emetic regimen to improve the quality-of-life for breast cancer patients. Citation Format: Nicole F Laslett, Dillon D McCourt, Kinjal Parikh, John F Kennedy, Zonera A Ali, Erik L Zeger, Aarti L Shevade, Tracey L Evans, Paul B Gilman, Margaretha Wallon. MyNauseaRisk assay - Predicting chemotherapy-induced delayed nausea using a blood-based assay [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-12.