Cohen, PA;
Powell, A;
Böhm, S;
Gilks, CB;
Stewart, CJR;
Meniawy, TM;
Bulsara, M;
... Singh, N; + view all
(2019)
Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data.
Gynecologic Oncology
10.1016/j.ygyno.2019.04.679.
(In press).
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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 RESULTS: 877 patients were included from published and unpublished studies.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.
| Type: | Article |
|---|---|
| Title: | Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ygyno.2019.04.679 |
| Publisher version: | http://doi.org/10.1016/j.ygyno.2019.04.679 |
| Language: | English |
| Additional information: | Copyright © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Chemotherapy response score, High-grade serous tubo-ovarian cancer, Neoadjuvant chemotherapy, Prognosis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10075284 |
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