Abstract 1978: Circulating rare events as a biomarker of anti-tumoral effect of ketamine therapy in non-small cell lung cancer

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Abstract Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related mortality worldwide, with surgical resection (with or without adjuvant chemotherapy) often being the recommended treatment for resectable localized disease. However, even with curative-intent resections, 30% to 55% of localized NSCLC patients experience recurrence and will die from the disease. Tumor-associated cells detected in peripheral blood, referred to here as circulating rare events, are believed to play a key role in metastatic dissemination, underscoring their potential as indicators of treatment response and recurrence risk. Recent retrospective analyses have revealed that the use of intraoperative Ketamine (Ket) during primary tumor resection surgery is associated with a lower recurrence rate, suggesting a potential utility in cancer treatment beyond its approved indication as an adjunct anesthetic. The study presented here investigates the effects of different anesthetic protocols on circulating rare events in NSCLC patients, specifically comparing Ket and dexmedetomidine (Dex) (also commonly employed as an adjunct anesthetic), to assess whether Ket exhibits anti-tumor effects and modulates the systemic tumor environment. Peripheral blood samples (n=60) were collected from 22 early-stage NSCLC patients undergoing primary tumor resection, with samples taken preoperatively (before surgical incision and after surgical closure) and at a three-week follow-up. Circulating rare events were identified through advanced imaging and phenotypic analysis and validated by comparison to blood samples from normal donors, which served as controls. Results indicated no significant differences between the anesthetic agents in pre- and post-surgery samples; however, at the three-week follow-up, Ket was associated with a higher incidence of circulating rare events and an increase in a specific cellular phenotype consistent with endothelial cells. These findings suggest that Ket may influence tumor vasculature and enhance tumor shedding, which could lead to a better prognosis after tumor resection in lung cancer patients. This highlights the potential of Ket as a perioperative agent that modulates tumor biology, as demonstrated by increased rare cell detection, and supports further investigation into a possibly expanded role in surgical oncology for potential to improve long-term outcomes in NSCLC patients. Citation Format: Anya Shah, Stephanie Shishido, Jeremy Mason, George W. Fischer, David Amar, Dawn Desiderio, Joseph R. Scarpa, David R. Jones, Amitabh Gulati, Alessia Pedoto, Alessandro De Camilli, Cosmin Guaran, Jacob C. Jackson, Alexandra Lewis, Michelle Zanone, Lucy Nystrom, Howard Scher, Ethan Barnett, Joshua Mincer, Peter Kuhn. Circulating rare events as a biomarker of anti-tumoral effect of ketamine therapy in non-small cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1978.