The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Shigeki Kusamura, Pilar Adriana Torres Mesa, Antonello Cabras, Dario Baratti, Marcello Deraco

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Abstract

Background: We conducted a prognostic analysis of preoperative parameters and Ki-67 determination to develop selection criteria for cytoreductive surgery (CRS) and HIPEC in patients with diffuse malignant peritoneal mesothelioma (DMPM). Methods: DMPM patients treated with CRS and HIPEC at NCI of Milan participated in this study. Multivariate analysis was conducted using Cox proportional hazard model and conditional inference tree method to select independent predictors of overall survival (OS) from the followings pre-cytoreduction parameters: age, sex, ECOG performance status, Charlson comorbidity index, previous systemic chemotherapy, CA-125, histological subtype (epithelioid vs. biphasic/sarcomatoid), Ki-67 (determined with immunohistochemistry), and peritoneal cancer index (PCI). Results: A total of 117 patients (male/female: 67/50) with median age of 60.5 (range 22–75) years were included. Eighty-three patients had ECOG performance status = 0, median Charlson comorbidity index was 4 (range 2–9), and 102 cases had epithelioid subtype. Median Ki-67 was 5 % (range 1–60). Ninety-four (80.3 %) cases were optimally cytoreduced. The Cox analysis identified Ki-67, PCI, and histological subtype as independent prognosticators of OS. Conditional inference tree method identified three prognostic subsets: (I) Ki-67 ≤ 9 %; (II) Ki-67 > 9 % and PCI ≤ 17; and (III) Ki-67 > 9 % and PCI > 17. The median OS for subsets I, II, and III were, 86.6, 63.2, and 10.3 months, respectively. Conclusions: Ki-67 is a powerful prognosticator that allows, along with PCI, and histological subtype, a good prediction of OS in patients with DMPM. Patients with Ki-67 > 9 % and PCI > 17 are unlikely to benefit from the procedure and should be considered for other treatment protocols.

Original languageEnglish
JournalAnnals of Surgical Oncology
DOIs
Publication statusAccepted/In press - Nov 16 2015

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Drug Therapy
Neoplasms
Survival
Comorbidity
Clinical Protocols
Proportional Hazards Models
Patient Selection
Malignant Mesothelioma
Multivariate Analysis
Immunohistochemistry

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

@article{076cade3f1f64938a0090e8324319a25,
title = "The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)",
abstract = "Background: We conducted a prognostic analysis of preoperative parameters and Ki-67 determination to develop selection criteria for cytoreductive surgery (CRS) and HIPEC in patients with diffuse malignant peritoneal mesothelioma (DMPM). Methods: DMPM patients treated with CRS and HIPEC at NCI of Milan participated in this study. Multivariate analysis was conducted using Cox proportional hazard model and conditional inference tree method to select independent predictors of overall survival (OS) from the followings pre-cytoreduction parameters: age, sex, ECOG performance status, Charlson comorbidity index, previous systemic chemotherapy, CA-125, histological subtype (epithelioid vs. biphasic/sarcomatoid), Ki-67 (determined with immunohistochemistry), and peritoneal cancer index (PCI). Results: A total of 117 patients (male/female: 67/50) with median age of 60.5 (range 22–75) years were included. Eighty-three patients had ECOG performance status = 0, median Charlson comorbidity index was 4 (range 2–9), and 102 cases had epithelioid subtype. Median Ki-67 was 5 {\%} (range 1–60). Ninety-four (80.3 {\%}) cases were optimally cytoreduced. The Cox analysis identified Ki-67, PCI, and histological subtype as independent prognosticators of OS. Conditional inference tree method identified three prognostic subsets: (I) Ki-67 ≤ 9 {\%}; (II) Ki-67 > 9 {\%} and PCI ≤ 17; and (III) Ki-67 > 9 {\%} and PCI > 17. The median OS for subsets I, II, and III were, 86.6, 63.2, and 10.3 months, respectively. Conclusions: Ki-67 is a powerful prognosticator that allows, along with PCI, and histological subtype, a good prediction of OS in patients with DMPM. Patients with Ki-67 > 9 {\%} and PCI > 17 are unlikely to benefit from the procedure and should be considered for other treatment protocols.",
author = "Shigeki Kusamura and {Torres Mesa}, {Pilar Adriana} and Antonello Cabras and Dario Baratti and Marcello Deraco",
year = "2015",
month = "11",
day = "16",
doi = "10.1245/s10434-015-4962-9",
language = "English",
journal = "Annals of Surgical Oncology",
issn = "1068-9265",
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TY - JOUR

T1 - The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

AU - Kusamura, Shigeki

AU - Torres Mesa, Pilar Adriana

AU - Cabras, Antonello

AU - Baratti, Dario

AU - Deraco, Marcello

PY - 2015/11/16

Y1 - 2015/11/16

N2 - Background: We conducted a prognostic analysis of preoperative parameters and Ki-67 determination to develop selection criteria for cytoreductive surgery (CRS) and HIPEC in patients with diffuse malignant peritoneal mesothelioma (DMPM). Methods: DMPM patients treated with CRS and HIPEC at NCI of Milan participated in this study. Multivariate analysis was conducted using Cox proportional hazard model and conditional inference tree method to select independent predictors of overall survival (OS) from the followings pre-cytoreduction parameters: age, sex, ECOG performance status, Charlson comorbidity index, previous systemic chemotherapy, CA-125, histological subtype (epithelioid vs. biphasic/sarcomatoid), Ki-67 (determined with immunohistochemistry), and peritoneal cancer index (PCI). Results: A total of 117 patients (male/female: 67/50) with median age of 60.5 (range 22–75) years were included. Eighty-three patients had ECOG performance status = 0, median Charlson comorbidity index was 4 (range 2–9), and 102 cases had epithelioid subtype. Median Ki-67 was 5 % (range 1–60). Ninety-four (80.3 %) cases were optimally cytoreduced. The Cox analysis identified Ki-67, PCI, and histological subtype as independent prognosticators of OS. Conditional inference tree method identified three prognostic subsets: (I) Ki-67 ≤ 9 %; (II) Ki-67 > 9 % and PCI ≤ 17; and (III) Ki-67 > 9 % and PCI > 17. The median OS for subsets I, II, and III were, 86.6, 63.2, and 10.3 months, respectively. Conclusions: Ki-67 is a powerful prognosticator that allows, along with PCI, and histological subtype, a good prediction of OS in patients with DMPM. Patients with Ki-67 > 9 % and PCI > 17 are unlikely to benefit from the procedure and should be considered for other treatment protocols.

AB - Background: We conducted a prognostic analysis of preoperative parameters and Ki-67 determination to develop selection criteria for cytoreductive surgery (CRS) and HIPEC in patients with diffuse malignant peritoneal mesothelioma (DMPM). Methods: DMPM patients treated with CRS and HIPEC at NCI of Milan participated in this study. Multivariate analysis was conducted using Cox proportional hazard model and conditional inference tree method to select independent predictors of overall survival (OS) from the followings pre-cytoreduction parameters: age, sex, ECOG performance status, Charlson comorbidity index, previous systemic chemotherapy, CA-125, histological subtype (epithelioid vs. biphasic/sarcomatoid), Ki-67 (determined with immunohistochemistry), and peritoneal cancer index (PCI). Results: A total of 117 patients (male/female: 67/50) with median age of 60.5 (range 22–75) years were included. Eighty-three patients had ECOG performance status = 0, median Charlson comorbidity index was 4 (range 2–9), and 102 cases had epithelioid subtype. Median Ki-67 was 5 % (range 1–60). Ninety-four (80.3 %) cases were optimally cytoreduced. The Cox analysis identified Ki-67, PCI, and histological subtype as independent prognosticators of OS. Conditional inference tree method identified three prognostic subsets: (I) Ki-67 ≤ 9 %; (II) Ki-67 > 9 % and PCI ≤ 17; and (III) Ki-67 > 9 % and PCI > 17. The median OS for subsets I, II, and III were, 86.6, 63.2, and 10.3 months, respectively. Conclusions: Ki-67 is a powerful prognosticator that allows, along with PCI, and histological subtype, a good prediction of OS in patients with DMPM. Patients with Ki-67 > 9 % and PCI > 17 are unlikely to benefit from the procedure and should be considered for other treatment protocols.

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