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)

Our plain-English summary of 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), by S. Kusamura, P.A. Torres Mesa, A. Cabras, et al (Annals of Surgical Oncology, 2016).

The study

• Authors: S. Kusamura, P.A. Torres Mesa, A. Cabras, D. Baratti, M. Deraco
• Journal: Annals of Surgical Oncology
• Published: 2016;23(5):1468-73
• Cited by: 62 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This study looked back at 117 patients with diffuse malignant peritoneal mesothelioma, a cancer of the abdominal lining. All were treated in Milan from June 1996 to January 2014 with cytoreductive surgery plus heated chemotherapy inside the abdomen (HIPEC). The authors tested which factors known before cytoreduction (tumor removal) predicted overall survival. The factors were age, sex, performance status, other illnesses, previous chemotherapy, CA-125 (a blood marker), tumor subtype, Ki-67 (a marker of cell division) and the peritoneal cancer index (PCI). The PCI is a disease-extent score, taken once the abdomen was opened. Median overall survival was 37.3 months (95% confidence interval 31.4 to 43.1). Ki-67, PCI and subtype were each independently linked to survival. A decision-tree analysis split patients into three groups. Those with Ki-67 of 9% or less had a median survival of 86.6 months. Those with Ki-67 above 9% and PCI of 17 or less had 63.2 months. Those with Ki-67 above 9% and PCI above 17 had 10.3 months. The authors concluded that this last group is unlikely to benefit from the procedure. They noted the study was retrospective and small and needs outside validation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of prospectively collected data on patients at a single institution (survival prognostic study)
• Who was studied: 117 patients with diffuse malignant peritoneal mesothelioma (67 men, 50 women; median age 60.5) treated with cytoreductive surgery and HIPEC at the National Cancer Institute in Milan, Italy, June 1996 to January 2014
• Exposure: No asbestos exposure was studied. The factors examined were pre-cytoreduction parameters: age, sex, ECOG performance status, Charlson comorbidity index, previous systemic chemotherapy, preoperative CA-125, histological subtype (epithelioid vs biphasic/sarcomatoid), Ki-67 and peritoneal cancer index (PCI). The PCI was scored when the abdomen was opened at the start of the operation, not from CT scans.
• Main results:
  • For all 117 patients, median overall survival was 37.3 months (95% CI 31.4 to 43.1) and 5-year overall survival was 42%. There were 61 deaths.
  • 94 of 117 patients (80.3%) had optimal cytoreduction. The rate of severe (grade 3 to 5) complications and procedure-related deaths was 38.5%.
  • In the multivariate Cox analysis, Ki-67, PCI and histological subtype were independently associated with overall survival. Each 10-unit increase in Ki-67 was linked to a hazard ratio of 1.73 (95% CI 1.39 to 2.14). Each 10-unit increase in PCI was linked to a hazard ratio of 1.90 (95% CI 1.44 to 2.52). Histological subtype had a hazard ratio of 2.38 (95% CI 1.20 to 4.73).
  • The Cox model's ability to separate shorter from longer survivors (Harrell's c-index) was 0.74, which the authors called acceptable.
  • Low-risk group (Ki-67 of 9% or less): median overall survival 86.6 months. The figure shows 67 patients in this group. The results text gives 86.5 months.
  • Intermediate-risk group (Ki-67 above 9% and PCI of 17 or less): median overall survival 63.2 months. The figure shows 15 patients in this group.
  • High-risk group (Ki-67 above 9% and PCI above 17): median overall survival 10.3 months. The figure shows 32 patients in this group. The authors said this is equivalent to results with palliative systemic chemotherapy alone.
• The authors' conclusion: The authors concluded that Ki-67, together with PCI, accurately predicts overall survival in these patients. In their view, surgery plus HIPEC is not appropriate for patients with Ki-67 above 9% and PCI above 17, who are unlikely to benefit. They added that the results require external validation.
• Limitations the authors state:
  • The study was retrospective, had a limited sample size, and lacked external validation.
  • Other prognostic factors were left out because too many patients lacked the data: lymph node status, mitotic count and nuclear grade.
  • With only 15 biphasic/sarcomatoid cases, the decision tree could not reliably assess histological subtype.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Ki-67, Cytoreductive Surgery, Peritoneal Mesothelioma, HIPEC, Multivariate Analysis, Overall Survival, ECOG Performance Status, Chemotherapy.

Related studies

• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome — C. Ihemelandu, L. Bijelic, et al. (2015)
• Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) — G.H.C. Tan, C.S. Chia, et al. (2018)
• Cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for children, adolescents, and young adults: the first 50 cases — A. Hayes-Jordan, H. Green, et al. (2015)
• A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy — J.M. Baumgartner, T.G. Kwong, et al. (2016)
• Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry — K.I. Votanopoulos, P. Sugarbaker, et al. (2018)
• Conversion to Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma After Bidirectional Chemotherapy — F. Le Roy, M. Gelli, et al. (2017)

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