Feasibility of using the handheld MasSpec pen technology for intraoperative identification of ovarian cancer during tumor reductive surgery.
Authors: Fleming Nicole D. , Wolfe Charles A. , Keating Michael , Sans Marta , Rangel Kelly M. , Sunny Calvin , Westin Shannon Neville , Jazaeri Amir A. , Soliman Pamela T. , Taylor Jolyn Sharpe , Hillman Robert Tyler , How Jeffrey Andrew , Lawson Barrett , Sood Anil K , Eberlin Livia Schiavinato 
Published: June 2024

5573

Background: Primary treatment of advanced ovarian cancer includes both chemotherapy and tumor reductive surgery (TRS), with the best outcomes seen in those patients in whom complete gross resection can be achieved. Real-time identification of metastatic ovarian cancer lesions in vivo during TRS can be challenging following neoadjuvant chemotherapy (NACT). In this study, we investigated the feasibility of using the hand-held MasSpec Pen (MSP) technology for intraoperative molecular analysis and tissue identification of metastatic sites during ovarian cancer TRS. The MSP is an innovative hand-held probe coupled to a mass spectrometer that non-destructively analyzes the metabolic composition of tissues in <20 seconds. Methods: Patients with advanced high grade serous carcinoma (HGSC) who received NACT and were scheduled for interval TRS were consented prior to their surgery. An Orbitrap Exploris mass spectrometer equipped with a MSP source was placed ~5 m away from the operating table. The MSP device was produced in the Eberlin lab and sterilized on-site prior to surgical use. In vivo MSP measurements were performed by gynecologic oncology surgeons and ex vivomeasurements were made by clinical research personnel. For each surgical case, 6 tissue sites were analyzed intraoperatively at the discretion of the surgeon including the primary tumor, 3 distinct normal peritoneum sites, and two suspicious metastatic sites. Research analysis sites were marked with surgical ink for pathological analysis. Direct correlation of intraoperative molecular analysis was made with final pathologic results. The data was used to build statistical classifiers using the Lasso predictive model. Results: Forty-four patients with advanced HGSC underwent interval TRS with MSP analysis, yielding 93 unique MSP in vivo analyses. Median age was 62.5 years (range 32-85 years). Most patients were diagnosed with stage IV (53%) disease and ovarian cancer primaries (85%). Majority of interval TRS was performed after 3-4 cycles of NACT (71%). From our 93 in vivo MSP analyses, 75 samples were chosen as our training set, and 18 samples chosen for our testing set. The MSP profiles were characterized by high relative abundance of small metabolites and glycerophospholipids, and consistent with prior data from ex vivo tissues. We demonstrated feasibility of utilizing the hand-held MSP in vivo, with preliminary accuracy of 89% in our training set and 88% in our testing set to predict cancer versus non-cancer tissue samples using the Lasso predictive model compared to final pathology. Conclusions: Intraoperative data collection utilizing the hand-held MSP is feasible and can be used in combination with statistical classifiers for real time disease-state diagnosis during TRS to distinguish ovarian cancer from normal tissues.