Paul A Cohen1, Aime Powell2, Steffen Böhm3, C Blake Gilks4, Colin J R Stewart5, Tarek M Meniawy6, Max Bulsara7, Stefanie Avril8, Eleanor C Brockbank9, Tjalling Bosse10, Gustavo Rubino de Azevedo Focchi11, Raji Ganesan12, Rosalind M Glasspool13, Brooke E Howitt14, Hyun-Soo Kim15, Jung-Yun Lee16, Nhu D Le17, Michelle Lockley18, Ranjit Manchanda19, Trupti Mandalia20, W Glenn McCluggage21, Iain McNeish22, Divya Midha23, Radhika Srinivasan24, Yun Yi Tan25, Rachael van der Griend26, Mayu Yunokawa27, Gian F Zannoni28, Naveena Singh29. 1. Department of Gynaecological Oncology, Bendat Family Comprehensive Cancer Centre, St John of God Subiaco Hospital, 12 Salvado Rd, Subiaco, Western Australia 6008, Australia; Division of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia; Institute for Health Research, The University of Notre Dame Australia, 32 Mouat Street Fremantle, Western Australia 6160, Australia. Electronic address: Paul.Cohen@uwa.edu.au. 2. Department of Gynaecological Oncology, Bendat Family Comprehensive Cancer Centre, St John of God Subiaco Hospital, 12 Salvado Rd, Subiaco, Western Australia 6008, Australia; Institute for Health Research, The University of Notre Dame Australia, 32 Mouat Street Fremantle, Western Australia 6160, Australia. 3. Department of Medical Oncology, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, United Kingdom. 4. Department of Anatomic Pathology, Vancouver General Hospital, 899 W 12th Ave, Vancouver, BC V5Z 1M9, Canada. 5. Department of Histopathology, King Edward Memorial Hospital, 374 Bagot Road, Subiaco, Western Australia 6008, Australia. 6. School of Medicine and Pharmacology, The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia; Department of Medical Oncology, Sir Charles Gairdner Hospital, Gairdner Drive Nedlands, Western Australia 6009, Australia. 7. Institute for Health Research, The University of Notre Dame Australia, 32 Mouat Street Fremantle, Western Australia 6160, Australia. 8. Department of Pathology, School of Medicine, Case Western Reserve University, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Wolstein Research Building, Room 6524, 2103 Cornell Road, Cleveland, OH 44106, United States of America; Institute of Pathology, Technische Universität München, Ismaninger Str. 22, Munich 81675, Germany. 9. Department of Gynaecological Oncology, Barts Health NHS Trust, Whitechapel Rd, London E1 1BB, United Kingdom. 10. Department of Pathology, Leiden University Medical Centre, Albinusdreef 2, PO Box 9600, 2333 ZA, Leiden, the Netherlands. 11. Department of Pathology, Federal University de São Paulo (UNIFESP), R Botucatu, 740, São Paulo, SP CEP 04023-062, Brazil. 12. Department of Cellular Pathology, Birmingham Women's NHS Foundation Trust, Mindelsohn Way, Birmingham B15 2TG, United Kingdom. 13. Cancer Research UK Clinical Trials Unit, Glasgow, The Beatson West of Scotland Cancer Centre, University of Glasgow, 1053 Great Western Road, Glasgow G12 0YN, United Kingdom. 14. Department of Pathology, School of Medicine, Stanford University, 300 Pasteur Drive, H2128E, Stanford, CA 94305, United States of America. 15. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea. 16. Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea. 17. Cancer Control Research, British Columbia Cancer Research Centre, 675 West 10th Ave, Vancouver, BC V5Z1L3, Canada. 18. Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom; University College London Hospital, 235 Euston Rd, Fitzrovia, London NW1 2BU, United Kingdom. 19. Department of Gynaecological Oncology, Barts Health NHS Trust, Royal London Hospital, 10th Floor, South Block, Whitechapel Road, London E1 1BB, United Kingdom. 20. Department of Histopathology, Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital (Wonford), Old Pathology Building, Church Lane, Exeter, Devon EX2 5AD, United Kingdom. 21. Department of Pathology, Belfast Health and Social Care Trust, Grosvenor Road Belfast, BT12 6BA, United Kingdom. 22. Division of Cancer, Department of Surgery and Cancer, Imperial College London, IRDB Building, Hammersmith Hospital, London W12 0NN, United Kingdom. 23. Department of Pathology, Tata Medical Center, 14 MAR, Rajarhat, Kolkata 700160, India. 24. Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India. 25. Department of Medical Oncology, Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, United Kingdom. 26. Department of Anatomical Pathology, Canterbury Health Laboratories, 2 Riccarton Ave, Christchurch 8011, New Zealand. 27. Department of Breast and Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. 28. Department of Pathology, Women and Child Health, Fondazione Policlinico Gemelli, Università Cattolica del Sacro Cuore, Largo F Vito 1, 00168 Roma, Italy. 29. Department of Cellular Pathology, Barts Health NHS Trust, Whitechapel Rd, London E1 1BB, United Kingdom.
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.
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.
Authors: Judith E den Ouden; Guido J R Zaman; Jelle Dylus; Antoon M van Doornmalen; Winfried R Mulder; Yvonne Grobben; Wilhelmina E van Riel; Joanne A de Hullu; Rogier C Buijsman; Anne M van Altena Journal: Oncotarget Date: 2020-12-08
Authors: Blair McNamara; Rosa Guerra; Jennifer Qin; Amaranta D Craig; Lee-May Chen; Madhulika G Varma; Jocelyn S Chapman Journal: Gynecol Oncol Rep Date: 2021-09-25
Authors: Premal H Thaker; William H Bradley; Charles A Leath; Camille Gunderson Jackson; Nicholas Borys; Khursheed Anwer; Lauren Musso; Junko Matsuzaki; Wiam Bshara; Kunle Odunsi; Ronald D Alvarez Journal: Clin Cancer Res Date: 2021-07-29 Impact factor: 13.801
Authors: Giuseppe Angelico; Antonio Ieni; Rosario Caltabiano; Angela Santoro; Frediano Inzani; Saveria Spadola; Giovanni Tuccari; Antonio Macrì; Gian Franco Zannoni Journal: Diagnostics (Basel) Date: 2021-03-05
Authors: M Liontos; A Andrikopoulou; K Koutsoukos; C Markellos; E Skafida; O Fiste; M Kaparelou; N Thomakos; D Haidopoulos; A Rodolakis; M A Dimopoulos; F Zagouri Journal: J Ovarian Res Date: 2021-11-01 Impact factor: 4.234