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 - Schmalfeldt, Barbara
AU - Weichert, W.
N1 - Publisher Copyright:
© 2019 The Authors
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 Results: 877 patients were included from published and unpublished studies.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 - Chemotherapy response score
KW - High-grade serous tubo-ovarian cancer
KW - Neoadjuvant chemotherapy
KW - Prognosis
UR - http://www.scopus.com/inward/record.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
SN - 0090-8258
VL - 154
SP - 441
EP - 448
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -