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

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 - 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, Nhu D

AU - Lockley, Michelle

AU - Manchanda, Ranjit

AU - Mandalia, Trupti

AU - McCluggage, W Glenn

AU - McNeish, Iain

AU - Midha, Divya

AU - Srinivasan, Radhika

AU - Tan, Yun Yi

AU - van der Griend, Rachael

AU - Yunokawa, Mayu

AU - Zannoni, Gian F

AU - Singh, Naveena

AU - HGSC CRS Collaborative Network (Supplementary 1)

N1 - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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CRS and progression free and overall survival (PFS and OS).RESULTS: 877 patients were included from published and unpublished studies.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.

KW - Antineoplastic Agents

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Biomarkers, Tumor/analysis

KW - Carboplatin/therapeutic use

KW - Disease-Free Survival

KW - Fallopian Tube Neoplasms/drug therapy

KW - Female

KW - Humans

KW - Neoadjuvant Therapy

KW - Neoplasms, Cystic, Mucinous, and Serous/drug therapy

KW - Ovarian Neoplasms/drug therapy

KW - Treatment Outcome

U2 - 10.1016/j.ygyno.2019.04.679

DO - 10.1016/j.ygyno.2019.04.679

M3 - SCORING: Review article

C2 - 31118141

VL - 154

SP - 441

EP - 448

JO - GYNECOL ONCOL

JF - GYNECOL ONCOL

SN - 0090-8258

IS - 2

ER -