Peter Hillemanns1,2, Pauline Wimberger1,3, Jessica Reif1,4, Herbert Stepp5, Rüdiger Klapdor2. 1. Department of Obstetrics and Gynecology, Ludwig-Maximilians-University Hospital, Munich, Germany. 2. Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany. 3. Department of Gynecology and Obstetrics, Technische Universität Dresden, Dresden, Germany. 4. Department of Obstetrics and Gynecology, Klinikum Starnberg, Starnberg, Germany. 5. LIFE-Center, Hospital of the University of Munich, Munich, Germany.
Abstract
OBJECTIVE: With a prospective feasibility study, we aimed to analyse the effect of different time points for application and dosage of preoperative oral 5-aminolevulinic acid administration for photodynamic diagnosis of peritoneal metastases in ovarian cancer patients. MATERIALS AND METHODS: In this prospective cohort study patients were randomly divided into three different groups. 5-Aminolevulinic acid was orally administered 3-14 hours before surgery using a dosage of 1 mg/kg, 4-9 hours using 10 mg/kg, and 9-16 hours using 10 mg/kg, respectively. Fluorescence was recorded intraoperatively using endoscopic equipment. The number and localization, of fluorescing nodules were documented. To analyze sensitivity and specificity samples from fluorescent and non-fluorescent tissues were evaluated histologically. Plasma protoporphyrin concentrations as well as any adverse events were assessed perioperatively. RESULTS: In total, 26 patients suspected for ovarian cancer underwent intraoperative photodynamic diagnosis with5-aminolevulinic acid. Most of them suffered from advanced cancer, 72% from FIGO-Stage IIIc. No severe adverse events were observed. Orally applied 5-aminolevulinic acid with a dosage of 1 mg/kg revealed no detectable fluorescence. However, at a dosage of 10 mg/kg fluorescence of metastatic tissue was significantly stronger than of non-affected tissue. If administered 4-9 hours preoperatively best detection rates for peritoneal metastases were obtained resulting in a sensitivity of 75% and a specificity of 100%. CONCLUSIONS: Photodynamic diagnosis with 5-aminolevulinic acid leads to safe and specific fluorescence detection of peritoneal metastases. 5-Aminolevulinic acid should be used at a dosage of at least 10 mg/kg 4-9 hours preoperatively. Further phase I-II studies are recommended. Lasers Surg. Med. 49:169-176, 2017.
RCT Entities:
OBJECTIVE: With a prospective feasibility study, we aimed to analyse the effect of different time points for application and dosage of preoperative oral 5-aminolevulinic acid administration for photodynamic diagnosis of peritoneal metastases in ovarian cancerpatients. MATERIALS AND METHODS: In this prospective cohort study patients were randomly divided into three different groups. 5-Aminolevulinic acid was orally administered 3-14 hours before surgery using a dosage of 1 mg/kg, 4-9 hours using 10 mg/kg, and 9-16 hours using 10 mg/kg, respectively. Fluorescence was recorded intraoperatively using endoscopic equipment. The number and localization, of fluorescing nodules were documented. To analyze sensitivity and specificity samples from fluorescent and non-fluorescent tissues were evaluated histologically. Plasma protoporphyrin concentrations as well as any adverse events were assessed perioperatively. RESULTS: In total, 26 patients suspected for ovarian cancer underwent intraoperative photodynamic diagnosis with 5-aminolevulinic acid. Most of them suffered from advanced cancer, 72% from FIGO-Stage IIIc. No severe adverse events were observed. Orally applied 5-aminolevulinic acid with a dosage of 1 mg/kg revealed no detectable fluorescence. However, at a dosage of 10 mg/kg fluorescence of metastatic tissue was significantly stronger than of non-affected tissue. If administered 4-9 hours preoperatively best detection rates for peritoneal metastases were obtained resulting in a sensitivity of 75% and a specificity of 100%. CONCLUSIONS: Photodynamic diagnosis with 5-aminolevulinic acid leads to safe and specific fluorescence detection of peritoneal metastases. 5-Aminolevulinic acid should be used at a dosage of at least 10 mg/kg 4-9 hours preoperatively. Further phase I-II studies are recommended. Lasers Surg. Med. 49:169-176, 2017.
Authors: Maciej Nowacki; Margarita Peterson; Tomasz Kloskowski; Eleanor McCabe; Delia Cortes Guiral; Karol Polom; Katarzyna Pietkun; Barbara Zegarska; Marta Pokrywczynska; Tomasz Drewa; Franco Roviello; Edward A Medina; Samy L Habib; Wojciech Zegarski Journal: Oncotarget Date: 2017-08-31