Development and validation of a prognostic nomogram for overall survival in patients with platinum-resistant ovarian cancer treated with chemotherapy.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
08 2019
Historique:
received: 13 03 2019
revised: 15 05 2019
accepted: 17 05 2019
pubmed: 7 7 2019
medline: 29 5 2020
entrez: 7 7 2019
Statut: ppublish

Résumé

Platinum-resistant ovarian cancer (PROC) is associated with a variable prognosis and unpredictable survival times. We have developed and validated a prognostic nomogram with the objective of improving the prediction of overall survival (OS) in patients treated with chemotherapy. The nomogram was developed using data from a training cohort of patients from two trials, including the chemotherapy-only arm in AURELIA and all randomised patients in CARTAXHY. Multivariable proportional hazards models were generated based on pretreatment characteristics to develop a nomogram that classifies patients based on OS. We subsequently assessed the performance of the nomogram in terms of discrimination and calibration in independent validation patient cohorts: PENELOPE and the bevacizumab-chemotherapy arm of AURELIA. The nomogram included six significant OS predictors, in order of importance: performance status, ascites, size of the largest tumour, CA-125, platinum-free interval and primary platinum resistance (C-statistic 0.69). In the training cohort, the median OS in the good, intermediate and poor prognosis groups was 25.3, 15.2 and 7.4 months, respectively. In the PENELOPE validation cohort (C-statistic 0.59), the median OS in the good, intermediate and poor prognosis groups was 18.5, 10.3 and 5.8 months, respectively. In the AURELIA bevacizumab-chemotherapy validation cohort (C-statistic 0.67), the median OS in good, intermediate and poor prognosis groups was 26.7, 13.8 and 10.0 months, respectively. This nomogram with six pretreatment characteristics allows prediction of OS in PROC and could be used for stratification of patients in clinical trials as well as for counselling patients about prognosis.

Sections du résumé

BACKGROUND
Platinum-resistant ovarian cancer (PROC) is associated with a variable prognosis and unpredictable survival times. We have developed and validated a prognostic nomogram with the objective of improving the prediction of overall survival (OS) in patients treated with chemotherapy.
METHODS
The nomogram was developed using data from a training cohort of patients from two trials, including the chemotherapy-only arm in AURELIA and all randomised patients in CARTAXHY. Multivariable proportional hazards models were generated based on pretreatment characteristics to develop a nomogram that classifies patients based on OS. We subsequently assessed the performance of the nomogram in terms of discrimination and calibration in independent validation patient cohorts: PENELOPE and the bevacizumab-chemotherapy arm of AURELIA.
RESULTS
The nomogram included six significant OS predictors, in order of importance: performance status, ascites, size of the largest tumour, CA-125, platinum-free interval and primary platinum resistance (C-statistic 0.69). In the training cohort, the median OS in the good, intermediate and poor prognosis groups was 25.3, 15.2 and 7.4 months, respectively. In the PENELOPE validation cohort (C-statistic 0.59), the median OS in the good, intermediate and poor prognosis groups was 18.5, 10.3 and 5.8 months, respectively. In the AURELIA bevacizumab-chemotherapy validation cohort (C-statistic 0.67), the median OS in good, intermediate and poor prognosis groups was 26.7, 13.8 and 10.0 months, respectively.
CONCLUSIONS
This nomogram with six pretreatment characteristics allows prediction of OS in PROC and could be used for stratification of patients in clinical trials as well as for counselling patients about prognosis.

Identifiants

pubmed: 31279306
pii: S0959-8049(19)30356-9
doi: 10.1016/j.ejca.2019.05.029
pii:
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Bevacizumab 2S9ZZM9Q9V
Topotecan 7M7YKX2N15
Carboplatin BG3F62OND5
pertuzumab K16AIQ8CTM
Paclitaxel P88XT4IS4D

Types de publication

Clinical Trial, Phase II Clinical Trial, Phase III Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't Validation Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

99-106

Informations de copyright

Copyright © 2019. Published by Elsevier Ltd.

Auteurs

Chee Khoon Lee (CK)

National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia. Electronic address: chee.lee@ctc.usyd.edu.au.

Rebecca Asher (R)

National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.

Michael Friedlander (M)

Medical Oncology, Prince of Wales Hospital, Sydney, Australia.

Val Gebski (V)

National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.

Antonio Gonzalez-Martin (A)

Grupo Español de Investigación en Cáncer de Ovario (GEICO) and MD Anderson Cancer Center Spain, Madrid, Spain; Clínica Universidad de Navarra, Madrid, Spain.

Alain Lortholary (A)

Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Medical Oncology, Hôpital Privé du Confluent S.A.S., Nantes, France.

Anne Lesoin (A)

GINECO and Medical Oncology, Centre Oscar Lambret, Lille, France.

Christian Kurzeder (C)

Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and Dept. of Gynecology & Gynecologic Oncology, Klinikum Essen Mitte, Essen, Germany.

Remy Largillier (R)

Centre Azuréen de Cancérologie, Mougins, France.

Felix Hilpert (F)

AGO and Dept. of Gynecology and Obstetrics, University Hospital Kiel, Kiel, Germany; Mammazentrum am Krankenhaus Jerusalem, Hamburg, Germany.

Anne-Claire Hardy-Bessard (AC)

GINECO and Medical Oncology, Centre Armoricain d'Oncologie, CARIO, Plérins sur mer, France.

Marie-Christine Kaminsky (MC)

GINECO and Medical Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-Lès-Nancy, France.

Andres Poveda (A)

GEICO and Instituto Valenciano de Oncología, Valencia, Spain.

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Classifications MeSH