Survival and modelled cancer antigen-125 ELIMination rate constant K score in ovarian cancer patients in first-line before poly(ADP-ribose) polymerase inhibitor era : A Gynaecologic Cancer Intergroup meta-analysis
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved..
BACKGROUND: In patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors.
METHODS: The dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (≥1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model.
RESULTS: KELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41-0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45-0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, ∼45.0, and 22.1 months) and PFS (58.1, ∼15.0, and 8.0 months). Surrogacy for OS and for PFS was not established.
CONCLUSION: KELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:191 |
---|---|
Enthalten in: |
European journal of cancer (Oxford, England : 1990) - 191(2023) vom: 04. Sept., Seite 112966 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Corbaux, Pauline [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 29.08.2023 Date Revised 20.03.2024 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.ejca.2023.112966 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM360426255 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM360426255 | ||
003 | DE-627 | ||
005 | 20240320233326.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.ejca.2023.112966 |2 doi | |
028 | 5 | 2 | |a pubmed24n1337.xml |
035 | |a (DE-627)NLM360426255 | ||
035 | |a (NLM)37542936 | ||
035 | |a (PII)S0959-8049(23)00318-0 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Corbaux, Pauline |e verfasserin |4 aut | |
245 | 1 | 0 | |a Survival and modelled cancer antigen-125 ELIMination rate constant K score in ovarian cancer patients in first-line before poly(ADP-ribose) polymerase inhibitor era |b A Gynaecologic Cancer Intergroup meta-analysis |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 29.08.2023 | ||
500 | |a Date Revised 20.03.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
520 | |a BACKGROUND: In patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors | ||
520 | |a METHODS: The dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (≥1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model | ||
520 | |a RESULTS: KELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41-0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45-0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, ∼45.0, and 22.1 months) and PFS (58.1, ∼15.0, and 8.0 months). Surrogacy for OS and for PFS was not established | ||
520 | |a CONCLUSION: KELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success | ||
650 | 4 | |a Meta-Analysis | |
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a CA-125 | |
650 | 4 | |a KELIM | |
650 | 4 | |a Ovarian cancer | |
650 | 4 | |a Primary chemosensitivity | |
650 | 4 | |a Prognostic biomarker | |
650 | 4 | |a Surrogate end-point | |
650 | 7 | |a Poly(ADP-ribose) Polymerase Inhibitors |2 NLM | |
650 | 7 | |a CA-125 Antigen |2 NLM | |
650 | 7 | |a Antineoplastic Agents |2 NLM | |
700 | 1 | |a You, Benoit |e verfasserin |4 aut | |
700 | 1 | |a Glasspool, Rosalind M |e verfasserin |4 aut | |
700 | 1 | |a Yanaihara, Nozomu |e verfasserin |4 aut | |
700 | 1 | |a Tinker, Anna V |e verfasserin |4 aut | |
700 | 1 | |a Lindemann, Kristina |e verfasserin |4 aut | |
700 | 1 | |a Ray-Coquard, Isabelle L |e verfasserin |4 aut | |
700 | 1 | |a Mirza, Mansoor R |e verfasserin |4 aut | |
700 | 1 | |a Subtil, Fabien |e verfasserin |4 aut | |
700 | 1 | |a Colomban, Olivier |e verfasserin |4 aut | |
700 | 1 | |a Péron, Julien |e verfasserin |4 aut | |
700 | 1 | |a Karamouza, Eleni |e verfasserin |4 aut | |
700 | 1 | |a McNeish, Iain |e verfasserin |4 aut | |
700 | 1 | |a Kelly, Caroline |e verfasserin |4 aut | |
700 | 1 | |a Kagimura, Tatsuo |e verfasserin |4 aut | |
700 | 1 | |a Welch, Stephen |e verfasserin |4 aut | |
700 | 1 | |a Lewsley, Liz-Anne |e verfasserin |4 aut | |
700 | 1 | |a Paoletti, Xavier |e verfasserin |4 aut | |
700 | 1 | |a Cook, Adrian |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t European journal of cancer (Oxford, England : 1990) |d 1991 |g 191(2023) vom: 04. Sept., Seite 112966 |w (DE-627)NLM012602779 |x 1879-0852 |7 nnns |
773 | 1 | 8 | |g volume:191 |g year:2023 |g day:04 |g month:09 |g pages:112966 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ejca.2023.112966 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 191 |j 2023 |b 04 |c 09 |h 112966 |