Peritoneal Surface Malignancies
Carlos HF Chan, MD, PhD
Associate Professor
Department of Surgery, University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Hannah Abigail Cooper A. Bank, MD PhD (she/her/hers)
Surgery Resident
Department of Surgery, Massachusetts General Hospital
boston, Massachusetts, United States
.jpg "Thinzar M. Lwin, MD (she/her/hers) photo")
Thinzar M. Lwin, MD (she/her/hers)
Assistant Professor
Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, California, United States
Manna Chang, PhD
Principal Data Scientist
Lumicell, Inc, United States
Kate P. Smith, MPH
Senior Director of Clinical Affairs
Lumicell, Inc.
Hudson, Massachusetts, United States
Kate P. Smith, MPH
Senior Director of Clinical Affairs
Lumicell, Inc.
Hudson, Massachusetts, United States
Jorge Ferrer, PhD
Senior Vice President Clinical Research and Strategy
Lumicell, Inc., United States
James C. Cusack, MD
Associate Professor of Surgery
Division of General and Oncologic Surgery Department of Surgery, Massachusetts General Hospital, United States
James C. Cusack, MD
Associate Professor of Surgery
Division of General and Oncologic Surgery Department of Surgery, Massachusetts General Hospital, United States
Peritoneal surface malignancies (PSM) include peritoneal metastasis of various cancers, including colorectal and ovarian cancers, and mesothelioma. The completeness of resection of peritoneal metastases has a significant impact on survival. Here, we present a feasibility study using pegulicianine (PG), a cathepsin activatable fluorescence imaging agent, and a hand-held fluorescence imager, previously demonstrated in breast cancer to enhance detection of PSM during surgery, referred to as pegulicianine fluorescence guided surgery (pFGS). We have previously shown that malignant tissue over-expresses cathepsin. This study is designed to determine the optimal dose and timing of administration of PG and develop a tumor detection algorithm for identification of PSM intraoperatively using pFGS.
Methods:
Patients undergoing abdominal cytoreductive surgery (CRS) were eligible for the study. Fluorescence imaging was performed using the imager. During surgery, regions suspected to contain cancer and regions of normal tissue were imaged in vivo prior to injection of PG to collect background fluorescence. After initial imaging, PG was administered (n= 3 at 1.0 mg/kg, n= 3 at 1.5 mg/kg). The indicated regions of interest were serially imaged in vivo using fluorescence at every hour until the tissue was removed or the surgery concludes. Images were compared with histopathological results of the resected tissue and the tumor-to-normal tissue signal ratio (T:N) was calculated.
Results:
Interim analysis indicated that the mean (± standard deviation) T:N in the cohorts dosed at 1 mg/kg and 1.5 mg/kg were 1.65 (± 0.11) and 1.87 (± 0.09), respectively, indicating the feasibility of pFGS to detect cancer in vivo. Based on these results, two changes were made to the protocol: (1), enrollment was expanded to 12 additional patients, 6 at each dose of 1.5 mg/kg and 2 mg/kg, and (2) PG injection 1-3 hours before surgery to collect fluorescence images at longer time points.
Conclusions:
Initial results show promising T:N using pFGS in patients undergoing CRS indicating preferential activation of PG in analyzed tumor tissue. As the study is still ongoing, the optimal dosage, imaging timepoint and tumor detection algorithm will be determined once the cohorts at 1.5 mg/kg and 2.0 mg/kg complete enrollment.