Mesenchymal molecular subtype is an independent predictor of severe postoperative complications after primary debulking surgery for advanced ovarian cancer

Diogo Torres, Amanika Kumar, Jamie N Bakkum-Gamez, Amy L. Weaver, Michaela E. McGree, Chen Wang, Carrie L. Langstraat, William Arthur Cliby

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective: To evaluate the contribution of molecular subtype to 30-day postoperative complications and 90-day mortality after primary debulking surgery (PDS) in advanced stage high-grade serous ovarian cancer (HGSOC). Methods: Patients with stages III–IV HGSOC undergoing PDS from 1994 to 2011 with available molecular subtyping were included. Residual disease (RD) status was categorized as 0, 0.1–0.5, 0.6–1.0, or >1 cm. Surgical complexity scores were calculated as high, intermediate, or low as previously published. Postoperative complications were graded according to the modified Accordion classification 0–4 scale; severe was defined as grade ≥3. Molecular subtypes were derived from Agilent 4 × 44k tumor mRNA expression profiles and categorized as mesenchymal (MES) or non-mesenchymal (non-MES). Logistic regression modeling was used to assess associations. Results: Of 329 patients, 68.7% were stage IIIC, 80.5% had RD ≤1 cm, 28.0% had MES subtype, and 19.5% had a grade 3–4 complication; 90-day mortality was 5.8%. In univariate analysis, patients with MES subtype were more likely to have severe complications compared to non-MES (31.5 vs. 14.8%; OR 2.66, 95% CI 1.51–4.69; p < 0.001). MES subtype remained an independent predictor of complications (adjusted OR 2.14, 95% CI 1.17–3.92; p = 0.01) in a multivariable model which included ASA score, preoperative albumin, and surgical complexity. There was no statistical difference in 90-day mortality in patients with MES compared to non-MES subtype (7.6 vs. 5.1%; OR 1.54, 95% CI 0.59–4.05; p = 0.38). Conclusions: MES subtype is an independent predictor of severe postoperative morbidity and adds to the potential use of pre-operative molecular testing in planning primary treatment of patients with advanced ovarian cancer.

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

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Ovarian Neoplasms
Mortality
Albumins
Logistic Models
Morbidity
Messenger RNA
Neoplasms
Therapeutics

Keywords

  • MES
  • Mesenchymal
  • Molecular subtypes
  • Ovarian cancer
  • Postoperative complications

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Mesenchymal molecular subtype is an independent predictor of severe postoperative complications after primary debulking surgery for advanced ovarian cancer. / Torres, Diogo; Kumar, Amanika; Bakkum-Gamez, Jamie N; Weaver, Amy L.; McGree, Michaela E.; Wang, Chen; Langstraat, Carrie L.; Cliby, William Arthur.

In: Gynecologic Oncology, 01.01.2018.

Research output: Contribution to journalArticle

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title = "Mesenchymal molecular subtype is an independent predictor of severe postoperative complications after primary debulking surgery for advanced ovarian cancer",
abstract = "Objective: To evaluate the contribution of molecular subtype to 30-day postoperative complications and 90-day mortality after primary debulking surgery (PDS) in advanced stage high-grade serous ovarian cancer (HGSOC). Methods: Patients with stages III–IV HGSOC undergoing PDS from 1994 to 2011 with available molecular subtyping were included. Residual disease (RD) status was categorized as 0, 0.1–0.5, 0.6–1.0, or >1 cm. Surgical complexity scores were calculated as high, intermediate, or low as previously published. Postoperative complications were graded according to the modified Accordion classification 0–4 scale; severe was defined as grade ≥3. Molecular subtypes were derived from Agilent 4 × 44k tumor mRNA expression profiles and categorized as mesenchymal (MES) or non-mesenchymal (non-MES). Logistic regression modeling was used to assess associations. Results: Of 329 patients, 68.7{\%} were stage IIIC, 80.5{\%} had RD ≤1 cm, 28.0{\%} had MES subtype, and 19.5{\%} had a grade 3–4 complication; 90-day mortality was 5.8{\%}. In univariate analysis, patients with MES subtype were more likely to have severe complications compared to non-MES (31.5 vs. 14.8{\%}; OR 2.66, 95{\%} CI 1.51–4.69; p < 0.001). MES subtype remained an independent predictor of complications (adjusted OR 2.14, 95{\%} CI 1.17–3.92; p = 0.01) in a multivariable model which included ASA score, preoperative albumin, and surgical complexity. There was no statistical difference in 90-day mortality in patients with MES compared to non-MES subtype (7.6 vs. 5.1{\%}; OR 1.54, 95{\%} CI 0.59–4.05; p = 0.38). Conclusions: MES subtype is an independent predictor of severe postoperative morbidity and adds to the potential use of pre-operative molecular testing in planning primary treatment of patients with advanced ovarian cancer.",
keywords = "MES, Mesenchymal, Molecular subtypes, Ovarian cancer, Postoperative complications",
author = "Diogo Torres and Amanika Kumar and Bakkum-Gamez, {Jamie N} and Weaver, {Amy L.} and McGree, {Michaela E.} and Chen Wang and Langstraat, {Carrie L.} and Cliby, {William Arthur}",
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T1 - Mesenchymal molecular subtype is an independent predictor of severe postoperative complications after primary debulking surgery for advanced ovarian cancer

AU - Torres, Diogo

AU - Kumar, Amanika

AU - Bakkum-Gamez, Jamie N

AU - Weaver, Amy L.

AU - McGree, Michaela E.

AU - Wang, Chen

AU - Langstraat, Carrie L.

AU - Cliby, William Arthur

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objective: To evaluate the contribution of molecular subtype to 30-day postoperative complications and 90-day mortality after primary debulking surgery (PDS) in advanced stage high-grade serous ovarian cancer (HGSOC). Methods: Patients with stages III–IV HGSOC undergoing PDS from 1994 to 2011 with available molecular subtyping were included. Residual disease (RD) status was categorized as 0, 0.1–0.5, 0.6–1.0, or >1 cm. Surgical complexity scores were calculated as high, intermediate, or low as previously published. Postoperative complications were graded according to the modified Accordion classification 0–4 scale; severe was defined as grade ≥3. Molecular subtypes were derived from Agilent 4 × 44k tumor mRNA expression profiles and categorized as mesenchymal (MES) or non-mesenchymal (non-MES). Logistic regression modeling was used to assess associations. Results: Of 329 patients, 68.7% were stage IIIC, 80.5% had RD ≤1 cm, 28.0% had MES subtype, and 19.5% had a grade 3–4 complication; 90-day mortality was 5.8%. In univariate analysis, patients with MES subtype were more likely to have severe complications compared to non-MES (31.5 vs. 14.8%; OR 2.66, 95% CI 1.51–4.69; p < 0.001). MES subtype remained an independent predictor of complications (adjusted OR 2.14, 95% CI 1.17–3.92; p = 0.01) in a multivariable model which included ASA score, preoperative albumin, and surgical complexity. There was no statistical difference in 90-day mortality in patients with MES compared to non-MES subtype (7.6 vs. 5.1%; OR 1.54, 95% CI 0.59–4.05; p = 0.38). Conclusions: MES subtype is an independent predictor of severe postoperative morbidity and adds to the potential use of pre-operative molecular testing in planning primary treatment of patients with advanced ovarian cancer.

AB - Objective: To evaluate the contribution of molecular subtype to 30-day postoperative complications and 90-day mortality after primary debulking surgery (PDS) in advanced stage high-grade serous ovarian cancer (HGSOC). Methods: Patients with stages III–IV HGSOC undergoing PDS from 1994 to 2011 with available molecular subtyping were included. Residual disease (RD) status was categorized as 0, 0.1–0.5, 0.6–1.0, or >1 cm. Surgical complexity scores were calculated as high, intermediate, or low as previously published. Postoperative complications were graded according to the modified Accordion classification 0–4 scale; severe was defined as grade ≥3. Molecular subtypes were derived from Agilent 4 × 44k tumor mRNA expression profiles and categorized as mesenchymal (MES) or non-mesenchymal (non-MES). Logistic regression modeling was used to assess associations. Results: Of 329 patients, 68.7% were stage IIIC, 80.5% had RD ≤1 cm, 28.0% had MES subtype, and 19.5% had a grade 3–4 complication; 90-day mortality was 5.8%. In univariate analysis, patients with MES subtype were more likely to have severe complications compared to non-MES (31.5 vs. 14.8%; OR 2.66, 95% CI 1.51–4.69; p < 0.001). MES subtype remained an independent predictor of complications (adjusted OR 2.14, 95% CI 1.17–3.92; p = 0.01) in a multivariable model which included ASA score, preoperative albumin, and surgical complexity. There was no statistical difference in 90-day mortality in patients with MES compared to non-MES subtype (7.6 vs. 5.1%; OR 1.54, 95% CI 0.59–4.05; p = 0.38). Conclusions: MES subtype is an independent predictor of severe postoperative morbidity and adds to the potential use of pre-operative molecular testing in planning primary treatment of patients with advanced ovarian cancer.

KW - MES

KW - Mesenchymal

KW - Molecular subtypes

KW - Ovarian cancer

KW - Postoperative complications

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