Phase I clinical trial of cytoreductive surgery and intraoperative intraperitoneal hyperthermic chemotherapy for the treatment of peritoneal carcinomatosis

e14119 Background: A select group of patients with peritoneal carcinomatosis (PC) has been treated with curative intent by cytoreductive surgery (CCS) associated with intraperitoneal hyperthermic chemotherapy (HIPEC). The objective of this study is to identify predictors of postoperative complications in patients undergoing CCS + HIPEC. Methods: We analyzed data from 136 procedures of CCS + HIPEC in 128 patients with PC, from March 2001 to December 2010. Variables clinical, surgical, and the scores obtained by rating scales of risk (ASA, POSSUM and ACE-27), were correlated with scores obtained by rating scales of morbidity and postoperative results (Bennett-Guerrero, NCI and McPeek). Carcinomatosis was caused by tumors of the appendix in 54 cases (39.7%), ovary in 43 (31.6%), colorectal in 22 (16.2%), peritoneal mesothelioma in 14 (10.3%) and others in three (2.2%). All patients were classified as ECOG 0 and 1 and had KPS> 80%. Complete cytoreduction (CC0) was performed in 93 (68.4%), CC1 30 (22.1%) and CC2 or CC3 in 13 (9.5%). Results: The rates of OS and the median follow-up were respectively 79.6% and 102 months for patients with CP of origin in tumors of the appendix, 78.6% and 74.8 months for source of peritoneal mesotheliomas, 73,9% and 55.9 months for ovarian origin and 36.4% and 31.1 months for colorectal origin. The morbidity (serious complications NCI - grade 3, 4, and 5) and postoperative mortality (30 days) were respectively 16.9% and 2.9%. The duration of surgery (> 9 hours) and ASA classification Scale (ASA class III) were the main predictors of postoperative complications in multivariate analysis. Age was a predictor of cardiovascular complications and one of the variables responsible for longer ICU stay. The number of anastomoses performed per procedure (2 or 3) was associated with the occurrence of infectious complications systemic and wound. Conclusions: The duration of surgery, ASA classification in scale, age and number of anastomoses were the factors most often related to the occurrence of severe postoperative complications after cytoreductive surgery associated with intraperitoneal hyperthermic chemotherapy.

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Multimodal fluorescence-guided surgery of colorectal peritoneal metastases, a phase I/II clinical trial.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps4119 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. TPS4119-TPS4119

Author(s):

Jan-Marie de Gooyer ◽

Fortuné Elekonawo ◽

Andre J.A. Bremers ◽

Otto Boerman ◽

Mark Rijpkema ◽

...

Keyword(s):

Clinical Trial ◽

Phase I ◽

Peritoneal Carcinomatosis ◽

Real Time ◽

Fluorescence Imaging ◽

Cytoreductive Surgery ◽

Peritoneal Metastases ◽

Colorectal Origin ◽

Intraoperative Fluorescence Imaging ◽

Intraoperative Fluorescence

TPS4119 Background: Successful treatment of patients with colorectal peritoneal carcinomatosis highly depends on complete surgical tumor resection of all tumor. Oncological outcomes can potentially be improved by intraoperative imaging using a tumor-targeting antibody conjugated to a fluorophore and a radiotracer. This enables preoperative radionuclide imaging, real-time intraoperative fluorescence imaging and gamma detection. In this study we investigate the feasibility, accuracy and safety of CEA-targeted preoperative SPECT/CT and intraoperative fluorescence imaging in patients with colorectal PC. Methods: In this phase I/II single arm protein dose escalation study patients with peritoneal metastases of colorectal origin who are scheduled for cytoreductive surgery and HIPEC will receive an intravenous injection of the CEA-targeting tracer 111In-DOTA-labetuzumab-IRDye800CW. The first 15 patients will receive a single dose of 2,10 or 50 mg 6 to 7 days prior to surgery. Four to five days after injection SPECT/CT imaging of the thorax and abdomen is performed to determine intra-abdominal tumor load and detect extra-abdominal metatases. At day 6/7 after injection, standard cytoreductive surgical resection extended with real-time near-infrared fluorescence imaging and radio guidance is performed. After surgery, the peritoneal cavity will be re-examined for residual disease with fluorescence imaging. Resected specimens are analyzed microscopically, immunohistochemically (CEA and H&E) and by gamma counting. Blood samples are drawn for farmacokinetics and safety analysis at 180 minutes, 4 days, 6 days and 3 weeks after tracer injection. In the phase II dose expansion cohort, 14 more patients will receive the optimal dose as determined in the phase I trial. The primary objectives of the trial are to assess the safety, feasibility and accuracy of preoperative SPECT/CT and intraoperative fluorescence imaging after administration of 111In- labetuzumab-IRDye800CW in patients with peritoneal carcinomatosis of colorectal origin who will undergo cytoreductive surgery and HIPEC. The secondary objectives are to assess whether additional malignant lesions can be visualized by fluorescence imaging after cytoreductive surgery, to assess the intensity of fluorescence in malignant and non-malignant tissue, to assess the correlation between localization of the dual-labeled antibody and CEA expression in tumor and healthy tissue and to determine blood concentrations of the dual labelled antibody at several time points in patients. Clinical trial information: NCT03699332 .

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