Development of the MasSpec Pen Technology to Guide Surgical Decisions in the Care for Patients with Ovarian Cancer

Summary: New technologies that provide molecular-based cancer detection and tissue identification are highly desirable to improve treatment for patients with cancer. High-grade serous ovarian cancer (HGSC) is the most common and lethal type of ovarian carcinoma, as most patients present with metastasis and advanced disease. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery has been increasingly used as the main treatment for patients. Yet, most patients do not achieve complete response to NACT and still have cancer at the time of surgery. Thus, gynecologic surgeons have the critical task of visually identifying and removing all residual tumor lesions during surgery— a task that can be very challenging due to the drastic changes that NACT causes to tumor tissue morphology. Inevitably, surgeons are faced with a difficult scenario: aggressively remove suspected tumor with surrounding healthy tissue; or leave suspected treated tumor behind. Moreover, many patients still present chemoresistant minimal residual disease (MRD) after NACT and surgery, leading to worse outcomes. These issues escalate health care costs, place patients at risk for morbidity, and negatively affect survival. To address these challenges, we developed the MasSpec Pen (MSPen) technology as an innovative approach for rapid and non-destructive intraoperative tissue analysis. The MSPen employs a droplet of water to directly extract lipids and metabolites from tissues, which are then immediately analyzed by mass spectrometry (MS) and statistical classifiers to identify tissues in seconds. In lab studies, we showed that the MSPen metabolic information allows identification of HGSC with 96% accuracy. In clinical studies, the MSPen was tested by surgeons intraoperatively for in vivo tissue identification and implemented in ovarian surgeries at MD Anderson Cancer Center (MDACC). Using MS imaging, we have further shown that metabolic data from ex vivo ovarian cancer tissues is related to NACT response. We hypothesize that the MSPen allows identification of pre- and post-NACT tumor tissue and MRD in vivo to guide surgical treatment, and reveals novel in vivo metabolic patterns related to NACT response and cancer persistence. Our aims are: Aim 1. Refine the MSPen technology for intraoperative HGSC detection in open surgeries. We will use a next-gen version of the MSPen to optimize performance for metastatic HGSC detection in primary (n=120) and interval debulking surgeries (n=200) and use the metabolic data from pre- and post-NACT HGSC tissues to refine statistical classifiers for metastatic HGSC detection; Aim 2. Develop the laparoscopic-MSPen for identification of MRD after NACT and surgery in second-look laparoscopies (n=100), in comparison to histopathology and circulating tumor DNA data from the same patients; Aim 3. Define metabolic markers of cancer persistence and response to NACT using the in vivo data obtained. We will also obtain ex vivo tissues from a subset of patients and leverage our expertise in MS imaging and spatial transcriptomics to further explore metabolic patterns of MRD. Our proposal has the potential to offer transformative benefits to surgeons in advancing the standard of care for patients with ovarian cancer. Project Number: 1R01CA306089-01 | Fiscal Year: 2025 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Livia Schiavinato Eberlin (+2 co-PIs) | Institution: BAYLOR COLLEGE OF MEDICINE, HOUSTON, TX | Award Amount: $697,317 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 ISB-D (02)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11246361