Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data

The HGSC CRS Collaborative Network (Supplementary 1), Investigators

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Objective: There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT. Methods: We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3–4 NACT cycles and >6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS). Results: 877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5–65) and 28 months (IQR 7–92) respectively. CRS3 was seen in 249 patients (28%). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0·55 (95% CI, 0·45–0·66; P < 0·001) and 0·65 (95% CI 0·50–0·85, P = 0·002) respectively; no heterogeneity was identified (PFS: Q = 6·42, P = 0·698, I2 = 0·0%; OS: Q = 6·89, P = 0·648, I2 = 0·0%). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0·027). Conclusions: CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design.

Original languageEnglish
Pages (from-to)441-448
Number of pages8
JournalGynecologic Oncology
Volume154
Issue number2
DOIs
Publication statusPublished - 2019 Aug

Fingerprint

Meta-Analysis
Carcinoma
Drug Therapy
Biomarkers
Disease-Free Survival
Decision Making
Odds Ratio
Clinical Trials
Mutation
Survival
Therapeutics
Population

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynaecology

Cite this

@article{0ffd2ca236694ab08ba3f36d4f9d207b,
title = "Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data",
abstract = "Objective: There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT. Methods: We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3–4 NACT cycles and >6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS). Results: 877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5–65) and 28 months (IQR 7–92) respectively. CRS3 was seen in 249 patients (28{\%}). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0·55 (95{\%} CI, 0·45–0·66; P < 0·001) and 0·65 (95{\%} CI 0·50–0·85, P = 0·002) respectively; no heterogeneity was identified (PFS: Q = 6·42, P = 0·698, I2 = 0·0{\%}; OS: Q = 6·89, P = 0·648, I2 = 0·0{\%}). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0·027). Conclusions: CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design.",
author = "{The HGSC CRS Collaborative Network (Supplementary 1)} and Investigators and Cohen, {Paul A.} and Aime Powell and Steffen B{\"o}hm and Gilks, {C. Blake} and Stewart, {Colin J.R.} and Meniawy, {Tarek M.} and Max Bulsara and Stefanie Avril and Brockbank, {Eleanor C.} and Tjalling Bosse and {de Azevedo Focchi}, {Gustavo Rubino} and Raji Ganesan and Glasspool, {Rosalind M.} and Howitt, {Brooke E.} and Kim, {Hyun Soo} and Lee, {Jung Yun} and Le, {N. D.} and Michelle Lockley and Ranjit Manchanda and Trupti Mandalia and McCluggage, {W. Glenn} and Iain McNeish and D. Midha and Radhika Srinivasan and Tan, {Yun Yi} and {van der Griend}, Rachael and Mayu Yunokawa and Zannoni, {Gian F.} and Simi Aggarwal and Holger Bronger and Brown, {Elizabeth B.} and Martin Buck and Bukhari, {Syed A.} and Edwina Coghlan and Nichola Cope and {de Almeida}, {Michelle Samora} and {De Kroon}, {Cornelius D.} and Andrew Dean and Devlin, {Michael John} and Ditzel, {Helena M.} and E. Drecoll and Anna Fagotti and Asma Faruqi and L. Feeney and Kavita Gupta and Ian Harley and Frediano Inzani and Jeyarajah, {Arjun R.} and Koay, {M. H.Eleanor} and Kroep, {Judith R.}",
year = "2019",
month = "8",
doi = "10.1016/j.ygyno.2019.04.679",
language = "English",
volume = "154",
pages = "441--448",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "2",

}

Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma : A systematic review and meta-analysis of individual patient data. / The HGSC CRS Collaborative Network (Supplementary 1); Investigators.

In: Gynecologic Oncology, Vol. 154, No. 2, 08.2019, p. 441-448.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma

T2 - A systematic review and meta-analysis of individual patient data

AU - The HGSC CRS Collaborative Network (Supplementary 1)

AU - Investigators

AU - Cohen, Paul A.

AU - Powell, Aime

AU - Böhm, Steffen

AU - Gilks, C. Blake

AU - Stewart, Colin J.R.

AU - Meniawy, Tarek M.

AU - Bulsara, Max

AU - Avril, Stefanie

AU - Brockbank, Eleanor C.

AU - Bosse, Tjalling

AU - de Azevedo Focchi, Gustavo Rubino

AU - Ganesan, Raji

AU - Glasspool, Rosalind M.

AU - Howitt, Brooke E.

AU - Kim, Hyun Soo

AU - Lee, Jung Yun

AU - Le, N. D.

AU - Lockley, Michelle

AU - Manchanda, Ranjit

AU - Mandalia, Trupti

AU - McCluggage, W. Glenn

AU - McNeish, Iain

AU - Midha, D.

AU - Srinivasan, Radhika

AU - Tan, Yun Yi

AU - van der Griend, Rachael

AU - Yunokawa, Mayu

AU - Zannoni, Gian F.

AU - Aggarwal, Simi

AU - Bronger, Holger

AU - Brown, Elizabeth B.

AU - Buck, Martin

AU - Bukhari, Syed A.

AU - Coghlan, Edwina

AU - Cope, Nichola

AU - de Almeida, Michelle Samora

AU - De Kroon, Cornelius D.

AU - Dean, Andrew

AU - Devlin, Michael John

AU - Ditzel, Helena M.

AU - Drecoll, E.

AU - Fagotti, Anna

AU - Faruqi, Asma

AU - Feeney, L.

AU - Gupta, Kavita

AU - Harley, Ian

AU - Inzani, Frediano

AU - Jeyarajah, Arjun R.

AU - Koay, M. H.Eleanor

AU - Kroep, Judith R.

PY - 2019/8

Y1 - 2019/8

N2 - Objective: There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT. Methods: We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3–4 NACT cycles and >6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS). Results: 877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5–65) and 28 months (IQR 7–92) respectively. CRS3 was seen in 249 patients (28%). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0·55 (95% CI, 0·45–0·66; P < 0·001) and 0·65 (95% CI 0·50–0·85, P = 0·002) respectively; no heterogeneity was identified (PFS: Q = 6·42, P = 0·698, I2 = 0·0%; OS: Q = 6·89, P = 0·648, I2 = 0·0%). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0·027). Conclusions: CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design.

AB - Objective: There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT. Methods: We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3–4 NACT cycles and >6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS). Results: 877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5–65) and 28 months (IQR 7–92) respectively. CRS3 was seen in 249 patients (28%). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0·55 (95% CI, 0·45–0·66; P < 0·001) and 0·65 (95% CI 0·50–0·85, P = 0·002) respectively; no heterogeneity was identified (PFS: Q = 6·42, P = 0·698, I2 = 0·0%; OS: Q = 6·89, P = 0·648, I2 = 0·0%). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0·027). Conclusions: CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design.

UR - http://www.scopus.com/inward/record.url?scp=85065775204&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065775204&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2019.04.679

DO - 10.1016/j.ygyno.2019.04.679

M3 - Review article

C2 - 31118141

AN - SCOPUS:85065775204

VL - 154

SP - 441

EP - 448

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 2

ER -