Factors that influence survival in high-grade serous ovarian cancer

A complex relationship between molecular subtype, disease dissemination, and operability

Diogo Torres, Chen Wang, Amanika Kumar, Jamie N Bakkum-Gamez, Amy L. Weaver, Michaela E. McGree, Gottfried E. Konecny, Ellen L Goode, William Arthur Cliby

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: To investigate the relationship between molecular subtype, intraperitoneal (IP) disease dissemination patterns, resectability, and overall survival (OS) in advanced high-grade serous ovarian cancer (HGSOC). Methods: Patients undergoing primary surgery for stage III-IV HGSOC at Mayo Clinic from 1994 to 2011 were categorized into three IP disease dissemination patterns: upper abdominal or miliary; lower abdominal; and pelvic. Residual disease was defined as 0 (RD0), 0.1–0.5, 0.6–1.0, or >1 cm. Molecular subtypes were derived from Agilent 4x44k tumor mRNA expression profiles and categorized as mesenchymal (MES) or non-mesenchymal (non-MES). Results: Operative and molecular data was available for 334 patients. Median OS was shorter in patients with MES compared to non-MES subtypes (34.2 vs 44.6 months; P = 0.009). Patients with MES subtype were more likely to have upper abdominal/miliary disease compared to non-MES subtype (90% vs. 72%, P < 0.001). For patients with upper abdominal/miliary disease, complete resection (RD0) was less common in MES compared to non-MES subtypes (11% vs. 27%, P = 0.004). On multivariable analysis, RD was the only factor associated with OS (P < 0.001). In patients with upper abdominal/miliary disease, though less commonly achieved, RD0 improved survival irrespective of molecular subtype (median OS of 69.2 and 57.9 months for MES and non-MES subtype). Conclusions: Our results support a paradigm in which molecular subtype is an important driver of dissemination pattern; this in turn impacts resectability and ultimately survival. Consequently mesenchymal subtype is associated with much lower rates of complete resection, though RD0 remains the most important independent predictor of survival.

Original languageEnglish (US)
JournalGynecologic Oncology
DOIs
StateAccepted/In press - Jan 1 2018

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Ovarian Neoplasms
Survival
Messenger RNA
Neoplasms

Keywords

  • Epithelial ovarian cancer
  • High-grade serous ovarian cancer
  • Mesenchymal
  • Molecular subtype
  • Residual disease
  • TCGA subtype

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

@article{2b689cb968c94772b8688e397b8c12a2,
title = "Factors that influence survival in high-grade serous ovarian cancer: A complex relationship between molecular subtype, disease dissemination, and operability",
abstract = "Objective: To investigate the relationship between molecular subtype, intraperitoneal (IP) disease dissemination patterns, resectability, and overall survival (OS) in advanced high-grade serous ovarian cancer (HGSOC). Methods: Patients undergoing primary surgery for stage III-IV HGSOC at Mayo Clinic from 1994 to 2011 were categorized into three IP disease dissemination patterns: upper abdominal or miliary; lower abdominal; and pelvic. Residual disease was defined as 0 (RD0), 0.1–0.5, 0.6–1.0, or >1 cm. Molecular subtypes were derived from Agilent 4x44k tumor mRNA expression profiles and categorized as mesenchymal (MES) or non-mesenchymal (non-MES). Results: Operative and molecular data was available for 334 patients. Median OS was shorter in patients with MES compared to non-MES subtypes (34.2 vs 44.6 months; P = 0.009). Patients with MES subtype were more likely to have upper abdominal/miliary disease compared to non-MES subtype (90{\%} vs. 72{\%}, P < 0.001). For patients with upper abdominal/miliary disease, complete resection (RD0) was less common in MES compared to non-MES subtypes (11{\%} vs. 27{\%}, P = 0.004). On multivariable analysis, RD was the only factor associated with OS (P < 0.001). In patients with upper abdominal/miliary disease, though less commonly achieved, RD0 improved survival irrespective of molecular subtype (median OS of 69.2 and 57.9 months for MES and non-MES subtype). Conclusions: Our results support a paradigm in which molecular subtype is an important driver of dissemination pattern; this in turn impacts resectability and ultimately survival. Consequently mesenchymal subtype is associated with much lower rates of complete resection, though RD0 remains the most important independent predictor of survival.",
keywords = "Epithelial ovarian cancer, High-grade serous ovarian cancer, Mesenchymal, Molecular subtype, Residual disease, TCGA subtype",
author = "Diogo Torres and Chen Wang and Amanika Kumar and Bakkum-Gamez, {Jamie N} and Weaver, {Amy L.} and McGree, {Michaela E.} and Konecny, {Gottfried E.} and Goode, {Ellen L} and Cliby, {William Arthur}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.ygyno.2018.06.002",
language = "English (US)",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",

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TY - JOUR

T1 - Factors that influence survival in high-grade serous ovarian cancer

T2 - A complex relationship between molecular subtype, disease dissemination, and operability

AU - Torres, Diogo

AU - Wang, Chen

AU - Kumar, Amanika

AU - Bakkum-Gamez, Jamie N

AU - Weaver, Amy L.

AU - McGree, Michaela E.

AU - Konecny, Gottfried E.

AU - Goode, Ellen L

AU - Cliby, William Arthur

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objective: To investigate the relationship between molecular subtype, intraperitoneal (IP) disease dissemination patterns, resectability, and overall survival (OS) in advanced high-grade serous ovarian cancer (HGSOC). Methods: Patients undergoing primary surgery for stage III-IV HGSOC at Mayo Clinic from 1994 to 2011 were categorized into three IP disease dissemination patterns: upper abdominal or miliary; lower abdominal; and pelvic. Residual disease was defined as 0 (RD0), 0.1–0.5, 0.6–1.0, or >1 cm. Molecular subtypes were derived from Agilent 4x44k tumor mRNA expression profiles and categorized as mesenchymal (MES) or non-mesenchymal (non-MES). Results: Operative and molecular data was available for 334 patients. Median OS was shorter in patients with MES compared to non-MES subtypes (34.2 vs 44.6 months; P = 0.009). Patients with MES subtype were more likely to have upper abdominal/miliary disease compared to non-MES subtype (90% vs. 72%, P < 0.001). For patients with upper abdominal/miliary disease, complete resection (RD0) was less common in MES compared to non-MES subtypes (11% vs. 27%, P = 0.004). On multivariable analysis, RD was the only factor associated with OS (P < 0.001). In patients with upper abdominal/miliary disease, though less commonly achieved, RD0 improved survival irrespective of molecular subtype (median OS of 69.2 and 57.9 months for MES and non-MES subtype). Conclusions: Our results support a paradigm in which molecular subtype is an important driver of dissemination pattern; this in turn impacts resectability and ultimately survival. Consequently mesenchymal subtype is associated with much lower rates of complete resection, though RD0 remains the most important independent predictor of survival.

AB - Objective: To investigate the relationship between molecular subtype, intraperitoneal (IP) disease dissemination patterns, resectability, and overall survival (OS) in advanced high-grade serous ovarian cancer (HGSOC). Methods: Patients undergoing primary surgery for stage III-IV HGSOC at Mayo Clinic from 1994 to 2011 were categorized into three IP disease dissemination patterns: upper abdominal or miliary; lower abdominal; and pelvic. Residual disease was defined as 0 (RD0), 0.1–0.5, 0.6–1.0, or >1 cm. Molecular subtypes were derived from Agilent 4x44k tumor mRNA expression profiles and categorized as mesenchymal (MES) or non-mesenchymal (non-MES). Results: Operative and molecular data was available for 334 patients. Median OS was shorter in patients with MES compared to non-MES subtypes (34.2 vs 44.6 months; P = 0.009). Patients with MES subtype were more likely to have upper abdominal/miliary disease compared to non-MES subtype (90% vs. 72%, P < 0.001). For patients with upper abdominal/miliary disease, complete resection (RD0) was less common in MES compared to non-MES subtypes (11% vs. 27%, P = 0.004). On multivariable analysis, RD was the only factor associated with OS (P < 0.001). In patients with upper abdominal/miliary disease, though less commonly achieved, RD0 improved survival irrespective of molecular subtype (median OS of 69.2 and 57.9 months for MES and non-MES subtype). Conclusions: Our results support a paradigm in which molecular subtype is an important driver of dissemination pattern; this in turn impacts resectability and ultimately survival. Consequently mesenchymal subtype is associated with much lower rates of complete resection, though RD0 remains the most important independent predictor of survival.

KW - Epithelial ovarian cancer

KW - High-grade serous ovarian cancer

KW - Mesenchymal

KW - Molecular subtype

KW - Residual disease

KW - TCGA subtype

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