Prognostic value of molecular response via ctDNA measurement in predicating response of systemic therapy in patients with advanced solid cancer. Journal of Clinical Oncology

e13001Background: Molecular profiling of cancer can guide treatment decision, monitor response and predict clinical outcome in the era of precision medicine and individualized treatment. Emerging evidence has suggested that ctDNA change correlates with treatment response and predates radiological relapse. Thus, we aim to provide real-world data regarding the dynamic changes of ctDNA level measured via Guardant 360 Response in advanced solid cancer correlates with clinical outcome. Methods: We retrospectively reviewed data of patients with advanced solid cancer and had at least 2 timepoints of Guardant 360 Response test at Houston Methodist Cancer center from 1/1/2014- 2 /1/2022. Data collected included age, gender, type of solid cancer, mutational values, treatment started date and type of systemic therapy. Personalized mutational profiles derived from tumor tissue via whole-exome sequencing were used to design patient-specific ctDNA assays for variant detection in plasma samples. Blood samples taken at baseline and 8 weeks were analyzed to a 70-gene next-generation sequencing panel. On-therapy changes in circulating tumor DNA levels (molecular response) were measured using a ratio computation, with response defined as a decrease in mean variant allele fraction of 50% or more. Apart from ctDNA analysis, patients were also monitored using tumor markers and radiological imaging. Results: : Of 267 patients, only 93 were met the inclusions criteria with age 58.66 (±12.95) and female were the most with 77 (82.80%). Patients with breast cancer were the dominant with 62 (66.67%), Lung adenocarcinoma 20 (21.51%), Uveal Melanoma 4 (4.30%), Colorectal Cancer and Lung Squamous Cell Carcinoma 2 (2.15 %) each, Large Cell Lung Carcinoma, Sarcoma and Thymic Carcinoma were 1(1.07%) each. Patients who received Chemotherapy /Immunotherapy were 38 (41.30%), Chemotherapy/Immunotherapy/Radiation therapy were 29 (31.52%), Immunotherapy 9 (9.78%), Chemotherapy/Immunotherapy/Targeted Therapy 2 (2.17%) and Targeted Therapy /Chemotherapy 3 (3.26%).Patients samples who correlated with clinical data were 89 (95.70%) and only 4 (4.30%) were not .Follow-up time 2.15 (interquartile range: 1.10-4.12) years, patients who still alive are 24 (25.81%), median survival time 2.4 (95% CI: 1.78-2.76) years. Conclusions: Our data demonstrated that molecular response evaluation using circulating tumor DNA as a noninvasive predictor of response to systemic therapy in addition to standard of care imaging in some solid cancer. Further prospective studies are needed to confirm the validation.