Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials
Individual patient data from two randomised trials comparing neoadjuvant chemotherapy with upfront debulking surgery in advanced tubo-ovarian cancer were analysed to examine long-term outcomes for patients and to identify any preferable therapeutic approaches for subgroup populations. We did a per-p...
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| Veröffentlicht in: | The lancet oncology 2018-12, Vol.19 (12), p.1680-1687 |
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| creator | Vergote, Ignace Coens, Corneel Nankivell, Matthew Kristensen, Gunnar B Parmar, Mahesh K B Jayson, Gordon C Swart, Ann Marie Verheijen, René McCluggage, W Glenn Perren, Tim Panici, Pierluigi Benedetti Kenter, Gemma Casado, Antonio Mendiola, Cesar Stuart, Gavin Reed, Nick S Kehoe, Sean Tropé G., Claes Dobbs, Stephen Essapen, Sharadah Hoskins, P. Van Baal, M. Twigg, Jeremy Van Der Burg, Maria E.L. Godfrey, Keith Lacave, Angel J. Redman, Charles Lotocki, R. Olaitan, Adeola Mosgaard, B. Rustin, G. Persic, Mojca Hogg, Martin Van Der Velden, J. Ledermann, J. Peter Sykes, Peter Sykes Hird, Vicky Sandvei R., R. Cruickshank, D.J. Ottevanger, P.B. Pearson, Sheila Hall, Marcia Bessette, P. Gerdin, E. Lopes, Tito Fish, Andrew Van Eygen, K. Floquet, A. Tholander, B. Gul, N. Gornall, Robert Luesley, David Symonds, Paul Poole, David McNeish, Ian Hocking, Mark Sammaraie, Al Speiser, P. Leblanc, E. De Oliveira, C.F. Grimshaw, R. Zola, P. Parkin, David Lamb, Martin Gillespie, Alan Hamid, Abdel Ahmed, Ahmed Perez, David Skailes, Geraldine Jones, Rachel Leeson, Simon Elit, L. Gotlieb, W. Crosse, Barbara Ridley, Paul Head, Anthony Nieto, Joaquin Awwad, Saif Brinkmann, Dirk Eustace, Damian Katsaros, D. Popadiuk, C. Redman, C. Chan, S. Marth, C. Lankaster, Kate Indrajit, Fernando Quigley, Mary Adeyemi, Olu McNally, Orla Tristam, Amanda Lee, Martin Counsell, R. Gleeson, N. Papadopoulos, A. Maggino, T. Ghatage, P. Vermorken, J.B. Petru, E Amant, F. |
| description | Individual patient data from two randomised trials comparing neoadjuvant chemotherapy with upfront debulking surgery in advanced tubo-ovarian cancer were analysed to examine long-term outcomes for patients and to identify any preferable therapeutic approaches for subgroup populations.
We did a per-protocol pooled analysis of individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial (NCT00003636) and the Medical Research Council Chemotherapy Or Upfront Surgery (CHORUS) trial (ISRCTN74802813). In the EORTC trial, eligible women had biopsy-proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV invasive epithelial tubo-ovarian carcinoma. In the CHORUS trial, inclusion criteria were similar to those of the EORTC trial, and women with apparent FIGO stage IIIA and IIIB disease were also eligible. The main aim of the pooled analysis was to show non-inferiority in overall survival with neoadjuvant chemotherapy compared with upfront debulking surgery, using the reverse Kaplan-Meier method. Tests for heterogeneity were based on Cochran's Q heterogeneity statistic.
Data for 1220 women were included in the pooled analysis, 670 from the EORTC trial and 550 from the CHORUS trial. 612 women were randomly allocated to receive upfront debulking surgery and 608 to receive neoadjuvant chemotherapy. Median follow-up was 7·6 years (IQR 6·0–9·6; EORTC, 9·2 years [IQR 7·3–10·4]; CHORUS, 5·9 years [IQR 4·3–7·4]). Median age was 63 years (IQR 56–71) and median size of the largest metastatic tumour at diagnosis was 8 cm (IQR 4·8–13·0). 55 (5%) women had FIGO stage II–IIIB disease, 831 (68%) had stage IIIC disease, and 230 (19%) had stage IV disease, with staging data missing for 104 (9%) women. In the entire population, no difference in median overall survival was noted between patients who underwent neoadjuvant chemotherapy and upfront debulking surgery (27·6 months [IQR 14·1–51·3] and 26·9 months [12·7–50·1], respectively; hazard ratio [HR] 0·97, 95% CI 0·86–1·09; p=0·586). Median overall survival for EORTC and CHORUS patients was significantly different at 30·2 months (IQR 15·7–53·7) and 23·6 months (10·5–46·9), respectively (HR 1·20, 95% CI 1·06–1·36; p=0·004), but was not heterogeneous (Cochran's Q, p=0·17). Women with stage IV disease had significantly better outcomes with neoadjuvant chemotherapy compared with upfront debulking surgery (median overall survival 24·3 months [IQR 14·1–47·6] and 2 |
| doi_str_mv | 10.1016/S1470-2045(18)30566-7 |
| format | Article |
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Coens, Corneel ; Nankivell, Matthew ; Kristensen, Gunnar B ; Parmar, Mahesh K B ; Jayson, Gordon C ; Swart, Ann Marie ; Verheijen, René ; McCluggage, W Glenn ; Perren, Tim ; Panici, Pierluigi Benedetti ; Kenter, Gemma ; Casado, Antonio ; Mendiola, Cesar ; Stuart, Gavin ; Reed, Nick S ; Kehoe, Sean ; Tropé G., Claes ; Dobbs, Stephen ; Essapen, Sharadah ; Hoskins, P. ; Van Baal, M. ; Twigg, Jeremy ; Van Der Burg, Maria E.L. ; Godfrey, Keith ; Lacave, Angel J. ; Redman, Charles ; Lotocki, R. ; Olaitan, Adeola ; Mosgaard, B. ; Rustin, G. ; Persic, Mojca ; Hogg, Martin ; Van Der Velden, J. ; Ledermann, J. ; Peter Sykes, Peter Sykes ; Hird, Vicky ; Sandvei R., R. ; Cruickshank, D.J. ; Ottevanger, P.B. ; Pearson, Sheila ; Hall, Marcia ; Bessette, P. ; Gerdin, E. ; Lopes, Tito ; Fish, Andrew ; Van Eygen, K. ; Floquet, A. ; Tholander, B. ; Gul, N. ; Gornall, Robert ; Luesley, David ; Symonds, Paul ; Poole, David ; McNeish, Ian ; Hocking, Mark ; Sammaraie, Al ; Speiser, P. ; Leblanc, E. ; De Oliveira, C.F. ; Grimshaw, R. ; Zola, P. ; Parkin, David ; Lamb, Martin ; Gillespie, Alan ; Hamid, Abdel ; Ahmed, Ahmed ; Perez, David ; Skailes, Geraldine ; Jones, Rachel ; Leeson, Simon ; Elit, L. ; Gotlieb, W. ; Crosse, Barbara ; Ridley, Paul ; Head, Anthony ; Nieto, Joaquin ; Awwad, Saif ; Brinkmann, Dirk ; Eustace, Damian ; Katsaros, D. ; Popadiuk, C. ; Redman, C. ; Chan, S. ; Marth, C. ; Lankaster, Kate ; Indrajit, Fernando ; Quigley, Mary ; Adeyemi, Olu ; McNally, Orla ; Tristam, Amanda ; Lee, Martin ; Counsell, R. ; Gleeson, N. ; Papadopoulos, A. ; Maggino, T. ; Ghatage, P. ; Vermorken, J.B. ; Petru, E ; Amant, F.</creator><creatorcontrib>Vergote, Ignace ; Coens, Corneel ; Nankivell, Matthew ; Kristensen, Gunnar B ; Parmar, Mahesh K B ; Jayson, Gordon C ; Swart, Ann Marie ; Verheijen, René ; McCluggage, W Glenn ; Perren, Tim ; Panici, Pierluigi Benedetti ; Kenter, Gemma ; Casado, Antonio ; Mendiola, Cesar ; Stuart, Gavin ; Reed, Nick S ; Kehoe, Sean ; Tropé G., Claes ; Dobbs, Stephen ; Essapen, Sharadah ; Hoskins, P. ; Van Baal, M. ; Twigg, Jeremy ; Van Der Burg, Maria E.L. ; Godfrey, Keith ; Lacave, Angel J. ; Redman, Charles ; Lotocki, R. ; Olaitan, Adeola ; Mosgaard, B. ; Rustin, G. ; Persic, Mojca ; Hogg, Martin ; Van Der Velden, J. ; Ledermann, J. ; Peter Sykes, Peter Sykes ; Hird, Vicky ; Sandvei R., R. ; Cruickshank, D.J. ; Ottevanger, P.B. ; Pearson, Sheila ; Hall, Marcia ; Bessette, P. ; Gerdin, E. ; Lopes, Tito ; Fish, Andrew ; Van Eygen, K. ; Floquet, A. ; Tholander, B. ; Gul, N. ; Gornall, Robert ; Luesley, David ; Symonds, Paul ; Poole, David ; McNeish, Ian ; Hocking, Mark ; Sammaraie, Al ; Speiser, P. ; Leblanc, E. ; De Oliveira, C.F. ; Grimshaw, R. ; Zola, P. ; Parkin, David ; Lamb, Martin ; Gillespie, Alan ; Hamid, Abdel ; Ahmed, Ahmed ; Perez, David ; Skailes, Geraldine ; Jones, Rachel ; Leeson, Simon ; Elit, L. ; Gotlieb, W. ; Crosse, Barbara ; Ridley, Paul ; Head, Anthony ; Nieto, Joaquin ; Awwad, Saif ; Brinkmann, Dirk ; Eustace, Damian ; Katsaros, D. ; Popadiuk, C. ; Redman, C. ; Chan, S. ; Marth, C. ; Lankaster, Kate ; Indrajit, Fernando ; Quigley, Mary ; Adeyemi, Olu ; McNally, Orla ; Tristam, Amanda ; Lee, Martin ; Counsell, R. ; Gleeson, N. ; Papadopoulos, A. ; Maggino, T. ; Ghatage, P. ; Vermorken, J.B. ; Petru, E ; Amant, F. ; EORTC ; MRC CHORUS study investigators</creatorcontrib><description>Individual patient data from two randomised trials comparing neoadjuvant chemotherapy with upfront debulking surgery in advanced tubo-ovarian cancer were analysed to examine long-term outcomes for patients and to identify any preferable therapeutic approaches for subgroup populations.
We did a per-protocol pooled analysis of individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial (NCT00003636) and the Medical Research Council Chemotherapy Or Upfront Surgery (CHORUS) trial (ISRCTN74802813). In the EORTC trial, eligible women had biopsy-proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV invasive epithelial tubo-ovarian carcinoma. In the CHORUS trial, inclusion criteria were similar to those of the EORTC trial, and women with apparent FIGO stage IIIA and IIIB disease were also eligible. The main aim of the pooled analysis was to show non-inferiority in overall survival with neoadjuvant chemotherapy compared with upfront debulking surgery, using the reverse Kaplan-Meier method. Tests for heterogeneity were based on Cochran's Q heterogeneity statistic.
Data for 1220 women were included in the pooled analysis, 670 from the EORTC trial and 550 from the CHORUS trial. 612 women were randomly allocated to receive upfront debulking surgery and 608 to receive neoadjuvant chemotherapy. Median follow-up was 7·6 years (IQR 6·0–9·6; EORTC, 9·2 years [IQR 7·3–10·4]; CHORUS, 5·9 years [IQR 4·3–7·4]). Median age was 63 years (IQR 56–71) and median size of the largest metastatic tumour at diagnosis was 8 cm (IQR 4·8–13·0). 55 (5%) women had FIGO stage II–IIIB disease, 831 (68%) had stage IIIC disease, and 230 (19%) had stage IV disease, with staging data missing for 104 (9%) women. In the entire population, no difference in median overall survival was noted between patients who underwent neoadjuvant chemotherapy and upfront debulking surgery (27·6 months [IQR 14·1–51·3] and 26·9 months [12·7–50·1], respectively; hazard ratio [HR] 0·97, 95% CI 0·86–1·09; p=0·586). Median overall survival for EORTC and CHORUS patients was significantly different at 30·2 months (IQR 15·7–53·7) and 23·6 months (10·5–46·9), respectively (HR 1·20, 95% CI 1·06–1·36; p=0·004), but was not heterogeneous (Cochran's Q, p=0·17). Women with stage IV disease had significantly better outcomes with neoadjuvant chemotherapy compared with upfront debulking surgery (median overall survival 24·3 months [IQR 14·1–47·6] and 21·2 months [10·0–36·4], respectively; HR 0·76, 95% CI 0·58–1·00; p=0·048; median progression-free survival 10·6 months [7·9–15·0] and 9·7 months [5·2–13·2], respectively; HR 0·77, 95% CI 0·59–1·00; p=0·049).
Long-term follow-up data substantiate previous results showing that neoadjuvant chemotherapy and upfront debulking surgery result in similar overall survival in advanced tubo-ovarian cancer, with better survival in women with stage IV disease with neoadjuvant chemotherapy. This pooled analysis, with long-term follow-up, shows that neoadjuvant chemotherapy is a valuable treatment option for patients with stage IIIC–IV tubo-ovarian cancer, particularly in patients with a high tumour burden at presentation or poor performance status.
National Cancer Institute and Vlaamse Liga tegen kanker (Flemish League against Cancer).</description><identifier>ISSN: 1470-2045</identifier><identifier>EISSN: 1474-5488</identifier><identifier>DOI: 10.1016/S1470-2045(18)30566-7</identifier><identifier>PMID: 30413383</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Aged ; Biopsy ; Chemotherapy ; Clinical trials ; Cytoreduction Surgical Procedures - adverse effects ; Cytoreduction Surgical Procedures - mortality ; Fallopian Tube Neoplasms - mortality ; Fallopian Tube Neoplasms - pathology ; Fallopian Tube Neoplasms - therapy ; Female ; Gynecologic Surgical Procedures - adverse effects ; Gynecologic Surgical Procedures - mortality ; Gynecology ; Humans ; Invasiveness ; Medical research ; Metastases ; Middle Aged ; Multicenter Studies as Topic ; Neoadjuvant Therapy - adverse effects ; Neoadjuvant Therapy - mortality ; Neoplasm Staging ; Obstetrics ; Ovarian cancer ; Ovarian carcinoma ; Ovarian Neoplasms - mortality ; Ovarian Neoplasms - pathology ; Ovarian Neoplasms - therapy ; Patients ; Peritoneal Neoplasms - mortality ; Peritoneal Neoplasms - pathology ; Peritoneal Neoplasms - therapy ; Progression-Free Survival ; Randomized Controlled Trials as Topic ; Risk Factors ; Studies ; Surgery ; Survival ; Time Factors ; Tumor Burden ; Tumors</subject><ispartof>The lancet oncology, 2018-12, Vol.19 (12), p.1680-1687</ispartof><rights>2018 Elsevier Ltd</rights><rights>Copyright © 2018 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Dec 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c506t-628d4d2ba6ab4f11c83c292d565ed9073ea33f38bd8c2037eac046d1509e90543</citedby><cites>FETCH-LOGICAL-c506t-628d4d2ba6ab4f11c83c292d565ed9073ea33f38bd8c2037eac046d1509e90543</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1470204518305667$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30413383$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vergote, Ignace</creatorcontrib><creatorcontrib>Coens, Corneel</creatorcontrib><creatorcontrib>Nankivell, Matthew</creatorcontrib><creatorcontrib>Kristensen, Gunnar B</creatorcontrib><creatorcontrib>Parmar, Mahesh K B</creatorcontrib><creatorcontrib>Jayson, Gordon C</creatorcontrib><creatorcontrib>Swart, Ann Marie</creatorcontrib><creatorcontrib>Verheijen, René</creatorcontrib><creatorcontrib>McCluggage, W Glenn</creatorcontrib><creatorcontrib>Perren, Tim</creatorcontrib><creatorcontrib>Panici, Pierluigi Benedetti</creatorcontrib><creatorcontrib>Kenter, Gemma</creatorcontrib><creatorcontrib>Casado, Antonio</creatorcontrib><creatorcontrib>Mendiola, Cesar</creatorcontrib><creatorcontrib>Stuart, Gavin</creatorcontrib><creatorcontrib>Reed, Nick S</creatorcontrib><creatorcontrib>Kehoe, Sean</creatorcontrib><creatorcontrib>Tropé G., Claes</creatorcontrib><creatorcontrib>Dobbs, Stephen</creatorcontrib><creatorcontrib>Essapen, Sharadah</creatorcontrib><creatorcontrib>Hoskins, P.</creatorcontrib><creatorcontrib>Van Baal, M.</creatorcontrib><creatorcontrib>Twigg, Jeremy</creatorcontrib><creatorcontrib>Van Der Burg, Maria E.L.</creatorcontrib><creatorcontrib>Godfrey, Keith</creatorcontrib><creatorcontrib>Lacave, Angel J.</creatorcontrib><creatorcontrib>Redman, Charles</creatorcontrib><creatorcontrib>Lotocki, R.</creatorcontrib><creatorcontrib>Olaitan, Adeola</creatorcontrib><creatorcontrib>Mosgaard, B.</creatorcontrib><creatorcontrib>Rustin, G.</creatorcontrib><creatorcontrib>Persic, Mojca</creatorcontrib><creatorcontrib>Hogg, Martin</creatorcontrib><creatorcontrib>Van Der Velden, J.</creatorcontrib><creatorcontrib>Ledermann, J.</creatorcontrib><creatorcontrib>Peter Sykes, Peter Sykes</creatorcontrib><creatorcontrib>Hird, Vicky</creatorcontrib><creatorcontrib>Sandvei R., R.</creatorcontrib><creatorcontrib>Cruickshank, D.J.</creatorcontrib><creatorcontrib>Ottevanger, P.B.</creatorcontrib><creatorcontrib>Pearson, Sheila</creatorcontrib><creatorcontrib>Hall, Marcia</creatorcontrib><creatorcontrib>Bessette, P.</creatorcontrib><creatorcontrib>Gerdin, E.</creatorcontrib><creatorcontrib>Lopes, Tito</creatorcontrib><creatorcontrib>Fish, Andrew</creatorcontrib><creatorcontrib>Van Eygen, K.</creatorcontrib><creatorcontrib>Floquet, A.</creatorcontrib><creatorcontrib>Tholander, B.</creatorcontrib><creatorcontrib>Gul, N.</creatorcontrib><creatorcontrib>Gornall, Robert</creatorcontrib><creatorcontrib>Luesley, David</creatorcontrib><creatorcontrib>Symonds, Paul</creatorcontrib><creatorcontrib>Poole, David</creatorcontrib><creatorcontrib>McNeish, Ian</creatorcontrib><creatorcontrib>Hocking, Mark</creatorcontrib><creatorcontrib>Sammaraie, Al</creatorcontrib><creatorcontrib>Speiser, P.</creatorcontrib><creatorcontrib>Leblanc, E.</creatorcontrib><creatorcontrib>De Oliveira, C.F.</creatorcontrib><creatorcontrib>Grimshaw, R.</creatorcontrib><creatorcontrib>Zola, P.</creatorcontrib><creatorcontrib>Parkin, David</creatorcontrib><creatorcontrib>Lamb, Martin</creatorcontrib><creatorcontrib>Gillespie, Alan</creatorcontrib><creatorcontrib>Hamid, Abdel</creatorcontrib><creatorcontrib>Ahmed, Ahmed</creatorcontrib><creatorcontrib>Perez, David</creatorcontrib><creatorcontrib>Skailes, Geraldine</creatorcontrib><creatorcontrib>Jones, Rachel</creatorcontrib><creatorcontrib>Leeson, Simon</creatorcontrib><creatorcontrib>Elit, L.</creatorcontrib><creatorcontrib>Gotlieb, W.</creatorcontrib><creatorcontrib>Crosse, Barbara</creatorcontrib><creatorcontrib>Ridley, Paul</creatorcontrib><creatorcontrib>Head, Anthony</creatorcontrib><creatorcontrib>Nieto, Joaquin</creatorcontrib><creatorcontrib>Awwad, Saif</creatorcontrib><creatorcontrib>Brinkmann, Dirk</creatorcontrib><creatorcontrib>Eustace, Damian</creatorcontrib><creatorcontrib>Katsaros, D.</creatorcontrib><creatorcontrib>Popadiuk, C.</creatorcontrib><creatorcontrib>Redman, C.</creatorcontrib><creatorcontrib>Chan, S.</creatorcontrib><creatorcontrib>Marth, C.</creatorcontrib><creatorcontrib>Lankaster, Kate</creatorcontrib><creatorcontrib>Indrajit, Fernando</creatorcontrib><creatorcontrib>Quigley, Mary</creatorcontrib><creatorcontrib>Adeyemi, Olu</creatorcontrib><creatorcontrib>McNally, Orla</creatorcontrib><creatorcontrib>Tristam, Amanda</creatorcontrib><creatorcontrib>Lee, Martin</creatorcontrib><creatorcontrib>Counsell, R.</creatorcontrib><creatorcontrib>Gleeson, N.</creatorcontrib><creatorcontrib>Papadopoulos, A.</creatorcontrib><creatorcontrib>Maggino, T.</creatorcontrib><creatorcontrib>Ghatage, P.</creatorcontrib><creatorcontrib>Vermorken, J.B.</creatorcontrib><creatorcontrib>Petru, E</creatorcontrib><creatorcontrib>Amant, F.</creatorcontrib><creatorcontrib>EORTC</creatorcontrib><creatorcontrib>MRC CHORUS study investigators</creatorcontrib><title>Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials</title><title>The lancet oncology</title><addtitle>Lancet Oncol</addtitle><description>Individual patient data from two randomised trials comparing neoadjuvant chemotherapy with upfront debulking surgery in advanced tubo-ovarian cancer were analysed to examine long-term outcomes for patients and to identify any preferable therapeutic approaches for subgroup populations.
We did a per-protocol pooled analysis of individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial (NCT00003636) and the Medical Research Council Chemotherapy Or Upfront Surgery (CHORUS) trial (ISRCTN74802813). In the EORTC trial, eligible women had biopsy-proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV invasive epithelial tubo-ovarian carcinoma. In the CHORUS trial, inclusion criteria were similar to those of the EORTC trial, and women with apparent FIGO stage IIIA and IIIB disease were also eligible. The main aim of the pooled analysis was to show non-inferiority in overall survival with neoadjuvant chemotherapy compared with upfront debulking surgery, using the reverse Kaplan-Meier method. Tests for heterogeneity were based on Cochran's Q heterogeneity statistic.
Data for 1220 women were included in the pooled analysis, 670 from the EORTC trial and 550 from the CHORUS trial. 612 women were randomly allocated to receive upfront debulking surgery and 608 to receive neoadjuvant chemotherapy. Median follow-up was 7·6 years (IQR 6·0–9·6; EORTC, 9·2 years [IQR 7·3–10·4]; CHORUS, 5·9 years [IQR 4·3–7·4]). Median age was 63 years (IQR 56–71) and median size of the largest metastatic tumour at diagnosis was 8 cm (IQR 4·8–13·0). 55 (5%) women had FIGO stage II–IIIB disease, 831 (68%) had stage IIIC disease, and 230 (19%) had stage IV disease, with staging data missing for 104 (9%) women. In the entire population, no difference in median overall survival was noted between patients who underwent neoadjuvant chemotherapy and upfront debulking surgery (27·6 months [IQR 14·1–51·3] and 26·9 months [12·7–50·1], respectively; hazard ratio [HR] 0·97, 95% CI 0·86–1·09; p=0·586). Median overall survival for EORTC and CHORUS patients was significantly different at 30·2 months (IQR 15·7–53·7) and 23·6 months (10·5–46·9), respectively (HR 1·20, 95% CI 1·06–1·36; p=0·004), but was not heterogeneous (Cochran's Q, p=0·17). Women with stage IV disease had significantly better outcomes with neoadjuvant chemotherapy compared with upfront debulking surgery (median overall survival 24·3 months [IQR 14·1–47·6] and 21·2 months [10·0–36·4], respectively; HR 0·76, 95% CI 0·58–1·00; p=0·048; median progression-free survival 10·6 months [7·9–15·0] and 9·7 months [5·2–13·2], respectively; HR 0·77, 95% CI 0·59–1·00; p=0·049).
Long-term follow-up data substantiate previous results showing that neoadjuvant chemotherapy and upfront debulking surgery result in similar overall survival in advanced tubo-ovarian cancer, with better survival in women with stage IV disease with neoadjuvant chemotherapy. This pooled analysis, with long-term follow-up, shows that neoadjuvant chemotherapy is a valuable treatment option for patients with stage IIIC–IV tubo-ovarian cancer, particularly in patients with a high tumour burden at presentation or poor performance status.
National Cancer Institute and Vlaamse Liga tegen kanker (Flemish League against Cancer).</description><subject>Aged</subject><subject>Biopsy</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Cytoreduction Surgical Procedures - adverse effects</subject><subject>Cytoreduction Surgical Procedures - mortality</subject><subject>Fallopian Tube Neoplasms - mortality</subject><subject>Fallopian Tube Neoplasms - pathology</subject><subject>Fallopian Tube Neoplasms - therapy</subject><subject>Female</subject><subject>Gynecologic Surgical Procedures - adverse effects</subject><subject>Gynecologic Surgical Procedures - mortality</subject><subject>Gynecology</subject><subject>Humans</subject><subject>Invasiveness</subject><subject>Medical research</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>Multicenter Studies as Topic</subject><subject>Neoadjuvant Therapy - adverse effects</subject><subject>Neoadjuvant Therapy - mortality</subject><subject>Neoplasm Staging</subject><subject>Obstetrics</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - mortality</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Ovarian Neoplasms - therapy</subject><subject>Patients</subject><subject>Peritoneal Neoplasms - mortality</subject><subject>Peritoneal Neoplasms - pathology</subject><subject>Peritoneal Neoplasms - therapy</subject><subject>Progression-Free Survival</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Risk Factors</subject><subject>Studies</subject><subject>Surgery</subject><subject>Survival</subject><subject>Time Factors</subject><subject>Tumor Burden</subject><subject>Tumors</subject><issn>1470-2045</issn><issn>1474-5488</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkc1u1DAUhSMEoqXwCCBLbMoirX8Thw1Co0IrVR2pP2vLsW9aD0kc7DjSPBDviWemsGDD6lrX37lH956ieE_wGcGkOr8jvMYlxVycEvmJYVFVZf2iOM5tXgou5cv9-4AcFW9i3GBMaoLF6-KIYU4Yk-y4-HUDXttNWvQ4I_MEg5-fIOhpixYIMUVkoU39Dzc-opjCI4QtciPSNvMGLJpT60u_6OD0iMyuF-JnNHnf50896n4bXUS-yyLrFmeT7tGkZwfZzepZoy74AWVLdLG-vV8hIZqaZKFFq8v17cMdmvPkPr4tXnW5wLvnelI8fLu4X12W1-vvV6uv16URuJrLikrLLW11pVveEWIkM7ShVlQCbINrBpqxjsnWSkMxq0EbzCtLBG6gwYKzk-L0MHcK_meCOKvBRQN9r0fwKSpKGKWU0YZl9OM_6MankDfeUaKWVAgsMyUOlAk-xgCdmoIbdNgqgtUuR7XPUe1CUkSqfY6qzroPz9NTO4D9q_oTXAa-HADI51gcBBVNvmrOxAUws7Le_cfiN9_IrZY</recordid><startdate>201812</startdate><enddate>201812</enddate><creator>Vergote, Ignace</creator><creator>Coens, Corneel</creator><creator>Nankivell, Matthew</creator><creator>Kristensen, Gunnar B</creator><creator>Parmar, Mahesh K B</creator><creator>Jayson, Gordon C</creator><creator>Swart, Ann Marie</creator><creator>Verheijen, René</creator><creator>McCluggage, W Glenn</creator><creator>Perren, Tim</creator><creator>Panici, Pierluigi Benedetti</creator><creator>Kenter, Gemma</creator><creator>Casado, Antonio</creator><creator>Mendiola, Cesar</creator><creator>Stuart, Gavin</creator><creator>Reed, Nick S</creator><creator>Kehoe, Sean</creator><creator>Tropé G., Claes</creator><creator>Dobbs, Stephen</creator><creator>Essapen, Sharadah</creator><creator>Hoskins, P.</creator><creator>Van Baal, M.</creator><creator>Twigg, Jeremy</creator><creator>Van Der Burg, Maria E.L.</creator><creator>Godfrey, Keith</creator><creator>Lacave, Angel J.</creator><creator>Redman, Charles</creator><creator>Lotocki, R.</creator><creator>Olaitan, Adeola</creator><creator>Mosgaard, B.</creator><creator>Rustin, G.</creator><creator>Persic, Mojca</creator><creator>Hogg, Martin</creator><creator>Van Der Velden, J.</creator><creator>Ledermann, J.</creator><creator>Peter Sykes, Peter Sykes</creator><creator>Hird, Vicky</creator><creator>Sandvei R., R.</creator><creator>Cruickshank, D.J.</creator><creator>Ottevanger, P.B.</creator><creator>Pearson, Sheila</creator><creator>Hall, Marcia</creator><creator>Bessette, P.</creator><creator>Gerdin, E.</creator><creator>Lopes, Tito</creator><creator>Fish, Andrew</creator><creator>Van Eygen, K.</creator><creator>Floquet, A.</creator><creator>Tholander, B.</creator><creator>Gul, N.</creator><creator>Gornall, Robert</creator><creator>Luesley, David</creator><creator>Symonds, Paul</creator><creator>Poole, David</creator><creator>McNeish, Ian</creator><creator>Hocking, Mark</creator><creator>Sammaraie, Al</creator><creator>Speiser, P.</creator><creator>Leblanc, E.</creator><creator>De Oliveira, C.F.</creator><creator>Grimshaw, R.</creator><creator>Zola, P.</creator><creator>Parkin, 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N.</creator><creator>Papadopoulos, A.</creator><creator>Maggino, T.</creator><creator>Ghatage, P.</creator><creator>Vermorken, J.B.</creator><creator>Petru, E</creator><creator>Amant, F.</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0TZ</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>201812</creationdate><title>Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials</title><author>Vergote, Ignace ; Coens, Corneel ; Nankivell, Matthew ; Kristensen, Gunnar B ; Parmar, Mahesh K B ; Jayson, Gordon C ; Swart, Ann Marie ; Verheijen, René ; McCluggage, W Glenn ; Perren, Tim ; Panici, Pierluigi Benedetti ; Kenter, Gemma ; Casado, Antonio ; Mendiola, Cesar ; Stuart, Gavin ; Reed, Nick S ; Kehoe, Sean ; Tropé G., Claes ; Dobbs, Stephen ; Essapen, Sharadah ; Hoskins, P. ; Van Baal, M. ; Twigg, Jeremy ; Van Der Burg, Maria E.L. ; Godfrey, Keith ; Lacave, Angel J. ; Redman, Charles ; Lotocki, R. ; Olaitan, Adeola ; Mosgaard, B. ; Rustin, G. ; Persic, Mojca ; Hogg, Martin ; Van Der Velden, J. ; Ledermann, J. ; Peter Sykes, Peter Sykes ; Hird, Vicky ; Sandvei R., R. ; Cruickshank, D.J. ; Ottevanger, P.B. ; Pearson, Sheila ; Hall, Marcia ; Bessette, P. ; Gerdin, E. ; Lopes, Tito ; Fish, Andrew ; Van Eygen, K. ; Floquet, A. ; Tholander, B. ; Gul, N. ; Gornall, Robert ; Luesley, David ; Symonds, Paul ; Poole, David ; McNeish, Ian ; Hocking, Mark ; Sammaraie, Al ; Speiser, P. ; Leblanc, E. ; De Oliveira, C.F. ; Grimshaw, R. ; Zola, P. ; Parkin, David ; Lamb, Martin ; Gillespie, Alan ; Hamid, Abdel ; Ahmed, Ahmed ; Perez, David ; Skailes, Geraldine ; Jones, Rachel ; Leeson, Simon ; Elit, L. ; Gotlieb, W. ; Crosse, Barbara ; Ridley, Paul ; Head, Anthony ; Nieto, Joaquin ; Awwad, Saif ; Brinkmann, Dirk ; Eustace, Damian ; Katsaros, D. ; Popadiuk, C. ; Redman, C. ; Chan, S. ; Marth, C. ; Lankaster, Kate ; Indrajit, Fernando ; Quigley, Mary ; Adeyemi, Olu ; McNally, Orla ; Tristam, Amanda ; Lee, Martin ; Counsell, R. ; Gleeson, N. ; Papadopoulos, A. ; Maggino, T. ; Ghatage, P. ; Vermorken, J.B. ; Petru, E ; Amant, F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c506t-628d4d2ba6ab4f11c83c292d565ed9073ea33f38bd8c2037eac046d1509e90543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Aged</topic><topic>Biopsy</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Cytoreduction Surgical Procedures - adverse effects</topic><topic>Cytoreduction Surgical Procedures - mortality</topic><topic>Fallopian Tube Neoplasms - mortality</topic><topic>Fallopian Tube Neoplasms - pathology</topic><topic>Fallopian Tube Neoplasms - therapy</topic><topic>Female</topic><topic>Gynecologic Surgical Procedures - adverse effects</topic><topic>Gynecologic Surgical Procedures - mortality</topic><topic>Gynecology</topic><topic>Humans</topic><topic>Invasiveness</topic><topic>Medical research</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Multicenter Studies as Topic</topic><topic>Neoadjuvant Therapy - adverse effects</topic><topic>Neoadjuvant Therapy - mortality</topic><topic>Neoplasm Staging</topic><topic>Obstetrics</topic><topic>Ovarian cancer</topic><topic>Ovarian carcinoma</topic><topic>Ovarian Neoplasms - mortality</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Ovarian Neoplasms - therapy</topic><topic>Patients</topic><topic>Peritoneal Neoplasms - mortality</topic><topic>Peritoneal Neoplasms - pathology</topic><topic>Peritoneal Neoplasms - therapy</topic><topic>Progression-Free Survival</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Risk Factors</topic><topic>Studies</topic><topic>Surgery</topic><topic>Survival</topic><topic>Time Factors</topic><topic>Tumor Burden</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vergote, Ignace</creatorcontrib><creatorcontrib>Coens, Corneel</creatorcontrib><creatorcontrib>Nankivell, Matthew</creatorcontrib><creatorcontrib>Kristensen, Gunnar B</creatorcontrib><creatorcontrib>Parmar, Mahesh K B</creatorcontrib><creatorcontrib>Jayson, Gordon C</creatorcontrib><creatorcontrib>Swart, Ann Marie</creatorcontrib><creatorcontrib>Verheijen, René</creatorcontrib><creatorcontrib>McCluggage, W Glenn</creatorcontrib><creatorcontrib>Perren, 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A.</creatorcontrib><creatorcontrib>Maggino, T.</creatorcontrib><creatorcontrib>Ghatage, P.</creatorcontrib><creatorcontrib>Vermorken, J.B.</creatorcontrib><creatorcontrib>Petru, E</creatorcontrib><creatorcontrib>Amant, F.</creatorcontrib><creatorcontrib>EORTC</creatorcontrib><creatorcontrib>MRC CHORUS study investigators</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest 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Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>The lancet oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vergote, Ignace</au><au>Coens, Corneel</au><au>Nankivell, Matthew</au><au>Kristensen, Gunnar B</au><au>Parmar, Mahesh K B</au><au>Jayson, Gordon C</au><au>Swart, Ann Marie</au><au>Verheijen, René</au><au>McCluggage, W Glenn</au><au>Perren, Tim</au><au>Panici, Pierluigi Benedetti</au><au>Kenter, Gemma</au><au>Casado, Antonio</au><au>Mendiola, Cesar</au><au>Stuart, Gavin</au><au>Reed, Nick S</au><au>Kehoe, Sean</au><au>Tropé G., Claes</au><au>Dobbs, Stephen</au><au>Essapen, Sharadah</au><au>Hoskins, P.</au><au>Van Baal, M.</au><au>Twigg, Jeremy</au><au>Van Der Burg, Maria E.L.</au><au>Godfrey, Keith</au><au>Lacave, Angel J.</au><au>Redman, Charles</au><au>Lotocki, R.</au><au>Olaitan, Adeola</au><au>Mosgaard, B.</au><au>Rustin, G.</au><au>Persic, Mojca</au><au>Hogg, Martin</au><au>Van Der Velden, J.</au><au>Ledermann, J.</au><au>Peter Sykes, Peter Sykes</au><au>Hird, Vicky</au><au>Sandvei R., R.</au><au>Cruickshank, D.J.</au><au>Ottevanger, P.B.</au><au>Pearson, Sheila</au><au>Hall, Marcia</au><au>Bessette, P.</au><au>Gerdin, E.</au><au>Lopes, Tito</au><au>Fish, Andrew</au><au>Van Eygen, K.</au><au>Floquet, A.</au><au>Tholander, B.</au><au>Gul, N.</au><au>Gornall, Robert</au><au>Luesley, David</au><au>Symonds, Paul</au><au>Poole, David</au><au>McNeish, Ian</au><au>Hocking, Mark</au><au>Sammaraie, Al</au><au>Speiser, P.</au><au>Leblanc, E.</au><au>De Oliveira, C.F.</au><au>Grimshaw, R.</au><au>Zola, P.</au><au>Parkin, David</au><au>Lamb, Martin</au><au>Gillespie, Alan</au><au>Hamid, Abdel</au><au>Ahmed, Ahmed</au><au>Perez, David</au><au>Skailes, Geraldine</au><au>Jones, Rachel</au><au>Leeson, Simon</au><au>Elit, L.</au><au>Gotlieb, W.</au><au>Crosse, Barbara</au><au>Ridley, Paul</au><au>Head, Anthony</au><au>Nieto, Joaquin</au><au>Awwad, Saif</au><au>Brinkmann, Dirk</au><au>Eustace, Damian</au><au>Katsaros, D.</au><au>Popadiuk, C.</au><au>Redman, C.</au><au>Chan, S.</au><au>Marth, C.</au><au>Lankaster, Kate</au><au>Indrajit, Fernando</au><au>Quigley, Mary</au><au>Adeyemi, Olu</au><au>McNally, Orla</au><au>Tristam, Amanda</au><au>Lee, Martin</au><au>Counsell, R.</au><au>Gleeson, N.</au><au>Papadopoulos, A.</au><au>Maggino, T.</au><au>Ghatage, P.</au><au>Vermorken, J.B.</au><au>Petru, E</au><au>Amant, F.</au><aucorp>EORTC</aucorp><aucorp>MRC CHORUS study investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials</atitle><jtitle>The lancet oncology</jtitle><addtitle>Lancet Oncol</addtitle><date>2018-12</date><risdate>2018</risdate><volume>19</volume><issue>12</issue><spage>1680</spage><epage>1687</epage><pages>1680-1687</pages><issn>1470-2045</issn><eissn>1474-5488</eissn><abstract>Individual patient data from two randomised trials comparing neoadjuvant chemotherapy with upfront debulking surgery in advanced tubo-ovarian cancer were analysed to examine long-term outcomes for patients and to identify any preferable therapeutic approaches for subgroup populations.
We did a per-protocol pooled analysis of individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial (NCT00003636) and the Medical Research Council Chemotherapy Or Upfront Surgery (CHORUS) trial (ISRCTN74802813). In the EORTC trial, eligible women had biopsy-proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV invasive epithelial tubo-ovarian carcinoma. In the CHORUS trial, inclusion criteria were similar to those of the EORTC trial, and women with apparent FIGO stage IIIA and IIIB disease were also eligible. The main aim of the pooled analysis was to show non-inferiority in overall survival with neoadjuvant chemotherapy compared with upfront debulking surgery, using the reverse Kaplan-Meier method. Tests for heterogeneity were based on Cochran's Q heterogeneity statistic.
Data for 1220 women were included in the pooled analysis, 670 from the EORTC trial and 550 from the CHORUS trial. 612 women were randomly allocated to receive upfront debulking surgery and 608 to receive neoadjuvant chemotherapy. Median follow-up was 7·6 years (IQR 6·0–9·6; EORTC, 9·2 years [IQR 7·3–10·4]; CHORUS, 5·9 years [IQR 4·3–7·4]). Median age was 63 years (IQR 56–71) and median size of the largest metastatic tumour at diagnosis was 8 cm (IQR 4·8–13·0). 55 (5%) women had FIGO stage II–IIIB disease, 831 (68%) had stage IIIC disease, and 230 (19%) had stage IV disease, with staging data missing for 104 (9%) women. In the entire population, no difference in median overall survival was noted between patients who underwent neoadjuvant chemotherapy and upfront debulking surgery (27·6 months [IQR 14·1–51·3] and 26·9 months [12·7–50·1], respectively; hazard ratio [HR] 0·97, 95% CI 0·86–1·09; p=0·586). Median overall survival for EORTC and CHORUS patients was significantly different at 30·2 months (IQR 15·7–53·7) and 23·6 months (10·5–46·9), respectively (HR 1·20, 95% CI 1·06–1·36; p=0·004), but was not heterogeneous (Cochran's Q, p=0·17). Women with stage IV disease had significantly better outcomes with neoadjuvant chemotherapy compared with upfront debulking surgery (median overall survival 24·3 months [IQR 14·1–47·6] and 21·2 months [10·0–36·4], respectively; HR 0·76, 95% CI 0·58–1·00; p=0·048; median progression-free survival 10·6 months [7·9–15·0] and 9·7 months [5·2–13·2], respectively; HR 0·77, 95% CI 0·59–1·00; p=0·049).
Long-term follow-up data substantiate previous results showing that neoadjuvant chemotherapy and upfront debulking surgery result in similar overall survival in advanced tubo-ovarian cancer, with better survival in women with stage IV disease with neoadjuvant chemotherapy. This pooled analysis, with long-term follow-up, shows that neoadjuvant chemotherapy is a valuable treatment option for patients with stage IIIC–IV tubo-ovarian cancer, particularly in patients with a high tumour burden at presentation or poor performance status.
National Cancer Institute and Vlaamse Liga tegen kanker (Flemish League against Cancer).</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30413383</pmid><doi>10.1016/S1470-2045(18)30566-7</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1470-2045 |
| ispartof | The lancet oncology, 2018-12, Vol.19 (12), p.1680-1687 |
| issn | 1470-2045 1474-5488 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2132223293 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Aged Biopsy Chemotherapy Clinical trials Cytoreduction Surgical Procedures - adverse effects Cytoreduction Surgical Procedures - mortality Fallopian Tube Neoplasms - mortality Fallopian Tube Neoplasms - pathology Fallopian Tube Neoplasms - therapy Female Gynecologic Surgical Procedures - adverse effects Gynecologic Surgical Procedures - mortality Gynecology Humans Invasiveness Medical research Metastases Middle Aged Multicenter Studies as Topic Neoadjuvant Therapy - adverse effects Neoadjuvant Therapy - mortality Neoplasm Staging Obstetrics Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - mortality Ovarian Neoplasms - pathology Ovarian Neoplasms - therapy Patients Peritoneal Neoplasms - mortality Peritoneal Neoplasms - pathology Peritoneal Neoplasms - therapy Progression-Free Survival Randomized Controlled Trials as Topic Risk Factors Studies Surgery Survival Time Factors Tumor Burden Tumors |
| title | Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T19%3A53%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Neoadjuvant%20chemotherapy%20versus%20debulking%20surgery%20in%20advanced%20tubo-ovarian%20cancers:%20pooled%20analysis%20of%20individual%20patient%20data%20from%20the%20EORTC%2055971%20and%20CHORUS%20trials&rft.jtitle=The%20lancet%20oncology&rft.au=Vergote,%20Ignace&rft.aucorp=EORTC&rft.date=2018-12&rft.volume=19&rft.issue=12&rft.spage=1680&rft.epage=1687&rft.pages=1680-1687&rft.issn=1470-2045&rft.eissn=1474-5488&rft_id=info:doi/10.1016/S1470-2045(18)30566-7&rft_dat=%3Cproquest_cross%3E2132223293%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2157825508&rft_id=info:pmid/30413383&rft_els_id=S1470204518305667&rfr_iscdi=true |