Cellular Mass Response to Therapy Correlates With Clinical Response for a Range of Malignancies.

Abstract

Cancer patients with advanced-stage disease have poor prognosis, typically having limited options for efficacious treatment, and genomics-based therapy guidance continues to benefit only a fraction of patients. Next-generation ex vivo approaches, such as cell mass-based response testing (MRT), offer an alternative precision medicine approach for a broader population of patients with cancer, but validation of clinical feasibility and potential impact remain necessary. We evaluated the clinical feasibility and accuracy of using live-cell MRT to predict patient drug sensitivity. Using a unified measurement workflow with a 48-hour result turnaround time, samples were subjected to MRT after treatment with a panel of drugs in vitro. After completion of therapeutic course, clinical response data were correlated with MRT-based predictions of outcome. Specimens were collected from 104 patients with solid (n = 69) and hematologic (n = 35) malignancies, using tissue formats including needle biopsies, malignant fluids, bone marrow aspirates, and blood samples. Of the 81 (78%) specimens qualified for MRT, 41 (51%) patients receiving physician-selected therapies had treatments matched to MRT. MRT demonstrated high concordance with clinical responses with an odds ratio (OR) of 14.80 (<i>P</i> = .0003 [95% CI, 2.83 to 102.9]). This performance held for both solid and hematologic malignances with ORs of 20.67 (<i>P</i> = .0128 [95% CI, 1.45 to 1,375.57]) and 8.20 (<i>P</i> = .045 [95% CI, 0.77 to 133.56]), respectively. Overall, these results had a predictive accuracy of 80% (<i>P</i> = .0026 [95% CI, 65 to 91]). MRT showed highly significant correlation with clinical response to therapy. Routine clinical use is technically feasible and broadly applicable to a wide range of samples and malignancy types, supporting the need for future validation studies.