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

Paul A.Cohen; AimePowell; SteffenBöhm; C.BlakeGilks; ColinJ.R.Stewart; TarekM.Meniawy; MaxBulsara; StefanieAvril; EleanorC.Brockbank; TjallingBosse; Gustavo RubinodeAzevedoFocchi; RajiGanesan; RosalindM.Glasspool; BrookeE.Howitt; Hyun-Soo Kim; Jung-Yun Lee; NhuD.Le; MichelleLockley; RanjitManchanda; TruptiMandalia; W.GlennMcCluggage; IainMcNeish; DivyaMidha; RadhikaSrinivasan; YunYiTan; RachaelvanderGriend; MayuYunokawa; GianF.Zannoni; The HGSCCRS Collaborative Network 
Takahiro Ebata af; NaveenaSingh ag; KenjiTamura ag; HiroshiYoshida

doi:10.1016/j.ygyno.2019.04.679

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

Authors: Paul A.Cohen ; AimePowell ; SteffenBöhm ; C.BlakeGilks ; ColinJ.R.Stewart ; TarekM.Meniawy ; MaxBulsara ; StefanieAvril ; EleanorC.Brockbank ; TjallingBosse ; Gustavo RubinodeAzevedoFocchi ; RajiGanesan ; RosalindM.Glasspool ; BrookeE.Howitt ; Hyun-Soo Kim ; Jung-Yun Lee ; NhuD.Le ; MichelleLockley ; RanjitManchanda ; TruptiMandalia ; W.GlennMcCluggage ; IainMcNeish ; DivyaMidha ; RadhikaSrinivasan ; YunYiTan ; RachaelvanderGriend ; MayuYunokawa ; GianF.Zannoni ; The HGSCCRS Collaborative Network Takahiro Ebata af ; NaveenaSingh ag ; KenjiTamura ag ; HiroshiYoshida

Citation: GYNECOLOGIC ONCOLOGY, Vol.154(2) : 441-448, 2019

Journal Title: GYNECOLOGIC ONCOLOGY

ISSN: 0090-8258

Issue Date: 2019

Keywords: Chemotherapy response score ; High-grade serous tubo-ovarian cancer ; Neoadjuvant chemotherapy ; Prognosis

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.