lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed and are posted here as part of a 12-month trial. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

Pathological Chemotherapy Response Score Predicts Survival in Patients with Advanced Ovarian Cancer Receiving Neoadjuvant Chemotherapy: Systematic Review and Meta-Analysis of Individual Patient Data

33 Pages Posted: 4 Dec 2018

See all articles by Paul Cohen

Paul Cohen

Bendat Family Comprehensive Cancer Centre - Department of Gynaecological Oncology; The University of Western Australia, Faculty of Medical and Health Sciences, Division of Obstetrics and Gynaecology; University of Notre Dame Australia - Institute for Health Research

Aime Powell

The University of Western Australia, Faculty of Medical and Health Sciences, Division of Obstetrics and Gynaecology; University of Notre Dame Australia - Institute for Health Research

Steffen Böhm

Barts Health NHS Trust, Department of Medical Oncology

C. Blake Gilks

Vancouver General Hospital - Department of Anatomic Pathology

Colin J.R. Stewart

King Edward Memorial Hospital - Department of Histopathology

Tarek M. Meniawy

The University of Western Australia - School of Medicine & Pharmacology; Sir Charles Gairdner Hospital - Department of Medical Oncology

Max Bulsara

University of Notre Dame Australia - Institute for Health Research

Stefanie Avril

Case Western Reserve University, School of Medicine, Department of Pathology; Technische Universität München (TUM) - Institute of Pathology

Elly C. Brockbank

Barts Health NHS Trust, Department of Gynaecological Oncology

Tjalling Bosse

Leiden University, Medical Center (LUMC), Department of Pathology

Gustavo Rubino de Azevedo Focchi

Federal University of São Paulo (Unifesp) - Department of Pathology

Raji Ganesan

Birmingham Women's NHS Foundation Trust, Department of Cellular Pathology

Rosalind M. Glasspool

University of Glasgow, College of Medical, Veterinary & Life Sciences, Beatson West of Scotland Cancer Centre, Cancer Research UK Clinical Trials Unit

Brooke E. Howitt

Stanford University - Department of Pathology

Hyun-Soo Kim

Yonsei University - College of Medicine

Jung-Yun Lee

Yonsei University - College of Medicine

Nhu D. Lee

British Columbia Cancer Research Centre

Michelle Lockley

Queen Mary University of London - Barts Cancer Institute

Ranchit Manchanda

Barts Health NHS Trust, Department of Gynaecological Oncology

Trupti Mandalia

Government of the United Kingdom - Royal Devon and Exeter Hospital

W. Glenn McCluggage

Belfast Health and Social Trust, Department of Pathology

Iain McNeish

Imperial College London - Department of Surgery and Cancer

Divya Midha

Tata Medical Center - Department of Pathology

Radhika Srinivasan

Postgraduate Institute of Medical Education and Research

Yun Yi Tan

University of Glasgow, College of Medical, Veterinary & Life Sciences, Beatson West of Scotland Cancer Centre, Department of Medical Oncology

Rachael van der Griend

Canterbury Health Laboratories - Department of Anatomical Pathology

Mayu Yunokawa

National Cancer Center Hospital - Department of Breast and Medical Oncology

Gian F. Zannoni

Catholic University of the Sacred Heart, Rome - Fondazione Policlinico Gemelli

HGSC CRS Collaborative Network

Independent

Naveena Singh

Barts Health NHS Trust, Department of Cellular Pathology

More...

Abstract

Background: The chemotherapy response score (CRS) has been recommended for reporting histological tumour response to neoadjuvant chemotherapy (NACT) in tubo-ovarian high-grade serous carcinoma (HGSC). The CRS reproducibly stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response. Studies have shown an association between CRS and progression-free survival (PFS) but not overall survival (OS).

Methods: We undertook a systematic review and meta-analysis and established an international collaboration to pool individual patient data (IPD) from 16 sites in 11 countries. All patients had stage IIIC/IV HGSC, received 3-4 NACT cycles and a minimum 6-month follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and PFS and OS.

Findings: 5 studies were identified that included 490 patients: 4 were at low-risk of bias. Unpublished IPD for 875 patients were obtained. 907 patients were included. Median PFS was 15 months (IQR 6-66) and median OS was 28 months (IQR 7-90). The pooled hazard ratio (HR) for PFS (CRS3 compared to CRS1/CRS2) was 0·52 (95%CI, 0·43 - 0·63; P <0·001). No heterogeneity was identified (Q=5·02, p<0·832, I2=0·0%). The pooled HR for OS (CRS3 compared to CRS1/CRS2) was 0·67 (95%CI 0·52 - 0·86, P= 0·001; Figure 2b). No heterogeneity was identified (Q=8·48, p<0·487, I2=0·0%).

Interpretation: CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This robust, reproducible biomarker can be incorporated into therapeutic decision-making and clinical trial design.

Funding: There was no funding source for this study.

Declaration of Interest: All authors declare no conflict of interest relevant to the submitted work.

Ethical Approval: Ethical approval was obtained (St John of God Healthcare Human Research Ethics Committee Reference 1291) for transfer of de-identified individual patient data from participating sites for statistical analysis at the Institute for Health Research, University of Notre Dame, Fremantle, Western Australia. Principal investigators at individual study sites obtained country-specific and local approvals.

Keywords: High grade serous carcinoma; ovarian cancer; chemotherapy response score; neoadjuvant chemotherapy; prognosis; biomarker

Suggested Citation

Cohen, Paul and Powell, Aime and Böhm, Steffen and Gilks, C. Blake and Stewart, Colin J.R. and Meniawy, Tarek M. and Bulsara, Max and Avril, Stefanie and Brockbank, Elly C. and Bosse, Tjalling and Focchi, Gustavo Rubino de Azevedo and Ganesan, Raji and Glasspool, Rosalind M. and Howitt, Brooke E. and Kim, Hyun-Soo and Lee, Jung-Yun and Lee, Nhu D. and Lockley, Michelle and Manchanda, Ranchit and Mandalia, Trupti and McCluggage, W. Glenn and McNeish, Iain and Midha, Divya and Srinivasan, Radhika and Tan, Yun Yi and van der Griend, Rachael and Yunokawa, Mayu and Zannoni, Gian F. and Network, HGSC CRS Collaborative and Singh, Naveena, Pathological Chemotherapy Response Score Predicts Survival in Patients with Advanced Ovarian Cancer Receiving Neoadjuvant Chemotherapy: Systematic Review and Meta-Analysis of Individual Patient Data (July 11, 2018). Available at SSRN: https://ssrn.com/abstract=3292601

Paul Cohen (Contact Author)

Bendat Family Comprehensive Cancer Centre - Department of Gynaecological Oncology ( email )

12 Salvado Road
Subiaco, Western Australia
Australia

The University of Western Australia, Faculty of Medical and Health Sciences, Division of Obstetrics and Gynaecology ( email )

Crawley, Western Australia
Australia

University of Notre Dame Australia - Institute for Health Research ( email )

32 Mouat Street
Fremantle, Western Australia
Australia

Aime Powell

The University of Western Australia, Faculty of Medical and Health Sciences, Division of Obstetrics and Gynaecology

Crawley, Western Australia
Australia

University of Notre Dame Australia - Institute for Health Research

32 Mouat Street
Fremantle, Western Australia
Australia

Steffen Böhm

Barts Health NHS Trust, Department of Medical Oncology

West Smithfield
London
United Kingdom

C. Blake Gilks

Vancouver General Hospital - Department of Anatomic Pathology

899 W 12th Ave
Vancouver, British Columbia
Canada

Colin J.R. Stewart

King Edward Memorial Hospital - Department of Histopathology

374 Bagot Rd
Subiaco, Western Australia
Australia

Tarek M. Meniawy

The University of Western Australia - School of Medicine & Pharmacology

Crawley, Western Australia
Australia

Sir Charles Gairdner Hospital - Department of Medical Oncology

Gairdner Drive
Nedlands, Western Australia
Australia

Max Bulsara

University of Notre Dame Australia - Institute for Health Research

32 Mouat Street
Fremantle, Western Australia
Australia

Stefanie Avril

Case Western Reserve University, School of Medicine, Department of Pathology

2511 Overlook Road
Cleveland Heights, OH
United States

Technische Universität München (TUM) - Institute of Pathology

Ismaninger Str. 22
Munich
Germany

Elly C. Brockbank

Barts Health NHS Trust, Department of Gynaecological Oncology

Whitechapel Road
London
United Kingdom

Tjalling Bosse

Leiden University, Medical Center (LUMC), Department of Pathology

Leiden
Netherlands

Gustavo Rubino de Azevedo Focchi

Federal University of São Paulo (Unifesp) - Department of Pathology

São Paulo
Brazil

Raji Ganesan

Birmingham Women's NHS Foundation Trust, Department of Cellular Pathology

Mindelsohn Way
Birmingham
United Kingdom

Rosalind M. Glasspool

University of Glasgow, College of Medical, Veterinary & Life Sciences, Beatson West of Scotland Cancer Centre, Cancer Research UK Clinical Trials Unit

1053 Great Western Road
Glasgow
United Kingdom

Brooke E. Howitt

Stanford University - Department of Pathology

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Hyun-Soo Kim

Yonsei University - College of Medicine

Korea, Republic of (South Korea)

Jung-Yun Lee

Yonsei University - College of Medicine

Korea, Republic of (South Korea)

Nhu D. Lee

British Columbia Cancer Research Centre

Michelle Lockley

Queen Mary University of London - Barts Cancer Institute

London, EC1M 6BQ
United Kingdom

Ranchit Manchanda

Barts Health NHS Trust, Department of Gynaecological Oncology

Whitechapel Road
London
United Kingdom

Trupti Mandalia

Government of the United Kingdom - Royal Devon and Exeter Hospital

Barrack Road
Exeter, Devon EX2 5DW
United Kingdom

W. Glenn McCluggage

Belfast Health and Social Trust, Department of Pathology

Belfast, Ireland
United Kingdom

Iain McNeish

Imperial College London - Department of Surgery and Cancer

London
United Kingdom

Divya Midha

Tata Medical Center - Department of Pathology

Kolkata
India

Radhika Srinivasan

Postgraduate Institute of Medical Education and Research

Sector 12
PGIMER, Sec. 12
Chandigarh, 160012
India

Yun Yi Tan

University of Glasgow, College of Medical, Veterinary & Life Sciences, Beatson West of Scotland Cancer Centre, Department of Medical Oncology

1053 Great Western Road
Glasgow
United Kingdom

Rachael Van der Griend

Canterbury Health Laboratories - Department of Anatomical Pathology

2 Riccarton Avenue
Christchurch
New Zealand

Mayu Yunokawa

National Cancer Center Hospital - Department of Breast and Medical Oncology

Tokyo
Japan

Gian F. Zannoni

Catholic University of the Sacred Heart, Rome - Fondazione Policlinico Gemelli

Rome
Italy

HGSC CRS Collaborative Network

Independent

No Address Available

Naveena Singh

Barts Health NHS Trust, Department of Cellular Pathology

Whitechapel Road
London
United Kingdom

Click here to go to TheLancet.com

Go to TheLancet.com

Paper statistics

Abstract Views
129
Downloads
23