Álvaro Arjona-Sánchez1,2, Ana Martínez-López3,4, Francisca Valenzuela-Molina5,3, Blanca Rufián-Andújar5,3, Sebastián Rufián-Peña5,3, Ángela Casado-Adam5,3, Juan Manuel Sánchez-Hidalgo5,3, Lidia Rodríguez-Ortiz5,3, Francisco Javier Medina-Fernández5,3, Cesar Díaz-López5,3, Melissa Granados-Rodríguez3, Rosa Ortega-Salas3,4, Justo P Castaño6, Manuel Tena-Sempere7, Javier Briceño-Delgado5, Antonio Romero-Ruíz5,3. 1. Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Córdoba, Spain. alvaroarjona@hotmail.com. 2. GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, ReinaCórdoba, Spain. alvaroarjona@hotmail.com. 3. GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, ReinaCórdoba, Spain. 4. Pathology Unit, Reina Sofia University Hospital, Córdoba, Spain. 5. Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Córdoba, Spain. 6. CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain. 7. CIBER Pathophysiology of Obesity and Nutrition, Carlos III Health Institute. Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.
Abstract
BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignancy, classified according to the Peritoneal Surface Oncology Group International (PSOGI) classification, whose response to treatment remains highly heterogeneous within the high-grade (HG) category. Molecular profiling of PMP cases might help to better categorize patients and predict treatment responses. METHODS: We studied the Ki-67 proliferation rate and P53 overexpression in tissue samples from our historical cohort of HG-PMP patients. We established as cut-off levels the third quartile of each marker to perform univariate and multivariate Cox regression survival analyses. According to these results, the HG-PMP category was divided into subcategories and a new survival analysis was performed. RESULTS: A total of 90/117 patients with PMP undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) were selected for secondary analysis. The survival analysis of the HG-PMP category for preoperative variables showed that a proliferation index defined by Ki-67 >15% is a bad prognostic factor, with a hazard ratio (HR) of 3.20 (95% confidence interval [CI] 1.24-8.25). Accordingly, the HG-PMP group was divided using the Ki-67 15% cut-off. The new PSOGI/Ki-67 variable was an independent prognostic factor for overall survival (OS), with an HR of 3.74 (95% CI 1.88-7.47), and disease-free survival (DFS), with an HR of 4.184 (95% CI 1.79-9.75). The estimated 5-year OS rate was 100%, 70% and 24% for the LG-PMP, HG-PMP ≤15% and HG-PMP >15% groups, respectively (p = 0.0001), while the 5-year DFS rate was 90%, 44% and 0%, respectively (p = 0.0001). CONCLUSION: Division of the HG-PMP category of the PSOGI classification, according to the Ki-67 proliferation index, provides two well-defined subcategories, with significant differences in terms of OS and DFS, and hence high prognostic value.
BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignancy, classified according to the Peritoneal Surface Oncology Group International (PSOGI) classification, whose response to treatment remains highly heterogeneous within the high-grade (HG) category. Molecular profiling of PMP cases might help to better categorize patients and predict treatment responses. METHODS: We studied the Ki-67 proliferation rate and P53 overexpression in tissue samples from our historical cohort of HG-PMP patients. We established as cut-off levels the third quartile of each marker to perform univariate and multivariate Cox regression survival analyses. According to these results, the HG-PMP category was divided into subcategories and a new survival analysis was performed. RESULTS: A total of 90/117 patients with PMP undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) were selected for secondary analysis. The survival analysis of the HG-PMP category for preoperative variables showed that a proliferation index defined by Ki-67 >15% is a bad prognostic factor, with a hazard ratio (HR) of 3.20 (95% confidence interval [CI] 1.24-8.25). Accordingly, the HG-PMP group was divided using the Ki-67 15% cut-off. The new PSOGI/Ki-67 variable was an independent prognostic factor for overall survival (OS), with an HR of 3.74 (95% CI 1.88-7.47), and disease-free survival (DFS), with an HR of 4.184 (95% CI 1.79-9.75). The estimated 5-year OS rate was 100%, 70% and 24% for the LG-PMP, HG-PMP ≤15% and HG-PMP >15% groups, respectively (p = 0.0001), while the 5-year DFS rate was 90%, 44% and 0%, respectively (p = 0.0001). CONCLUSION: Division of the HG-PMP category of the PSOGI classification, according to the Ki-67 proliferation index, provides two well-defined subcategories, with significant differences in terms of OS and DFS, and hence high prognostic value.
Authors: Shigeki Kusamura; Francesco Barretta; Yutaka Yonemura; Paul Hendrick Sugarbaker; Brendan John Moran; Edward A Levine; Diane Goere; Dario Baratti; Eran Nizri; David Lawson Morris; Olivier Glehen; Armando Sardi; Pedro Barrios; François Quénet; Laurent Villeneuve; Alberto Gómez-Portilla; Ignace de Hingh; Wim Ceelen; Joerg O W Pelz; Pompiliu Piso; Santiago González-Moreno; Kurt Van Der Speeten; Marcello Deraco Journal: JAMA Surg Date: 2021-03-10 Impact factor: 14.766
Authors: L Martín Román; P Lozano; D Baratti; S Kusamura; M Deraco; W Vásquez; L González Bayón Journal: Ann Surg Oncol Date: 2022-07-25 Impact factor: 4.339