Skip to main content
Erschienen in: Tumor Biology 12/2014

01.12.2014 | Research Article

Serum HE4 and CA125 as predictors of response and outcome during neoadjuvant chemotherapy of advanced high-grade serous ovarian cancer

verfasst von: Tuulia Vallius, Johanna Hynninen, Annika Auranen, Olli Carpén, Jaakko Matomäki, Sinikka Oksa, Johanna Virtanen, Seija Grénman

Erschienen in: Tumor Biology | Ausgabe 12/2014

Einloggen, um Zugang zu erhalten

Abstract

Human epididymis protein 4 (HE4) is a novel tumour marker in epithelial ovarian cancer (EOC). Data on its profile and predictive potential for subsequent outcome after neoadjuvant chemotherapy (NACT) are still under investigation. The aim of this study was to compare CA125 and HE4 profiles with radiologic response after NACT and to evaluate their potential as predictors of clinical outcome in a primarily inoperable EOC patient cohort. Twenty-five EOC patients of high-grade subtype (HGSC) treated with NACT were enrolled in the study. Serum HE4 and CA125 samples were taken at the time of diagnosis and before interval debulking surgery (IDS). Pre-NACT and pre-IDS HE4 and CA125 and their percentage changes were compared with NACT response seen on CT and surgical outcome in IDS. We also evaluated the biomarkers’ abilities to predict platinum-free interval (PFI), progression-free survival (PFS) and overall survival (OS). All 25 patients were considered inoperable in laparoscopy at the time of diagnosis. HE4 and CA125 changes during NACT did not correlate with the changes seen on CT. Surgical outcome in IDS was associated with pre-IDS biomarker values but not with those taken before diagnosis. In IDS, 87 % had <1-cm residual tumour. In patients with HE4 change >80 and <80 % during NACT, the median OS was 3.38 and 1.60 years (p = 0.01), respectively. Serum HE4 is a promising additional tool when evaluating advanced HGSC patient’s response to NACT. It may be helpful when deciding whether to proceed to IDS or to second-line chemotherapy.
Literatur
1.
Zurück zum Zitat Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363(10):943–53.CrossRef Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363(10):943–53.CrossRef
2.
Zurück zum Zitat Vergote I, Amant F, Kristensen G, Ehlen T, Reed NS, Casado A. Primary surgery or neoadjuvant chemotherapy followed by interval debulking surgery in advanced ovarian cancer. Eur J Cancer. 2011;47 Suppl 3:S88–92.CrossRef Vergote I, Amant F, Kristensen G, Ehlen T, Reed NS, Casado A. Primary surgery or neoadjuvant chemotherapy followed by interval debulking surgery in advanced ovarian cancer. Eur J Cancer. 2011;47 Suppl 3:S88–92.CrossRef
3.
Zurück zum Zitat Kang S, Nam BH. Does neoadjuvant chemotherapy increase optimal cytoreduction rate in advanced ovarian cancer? Meta-analysis of 21 studies. Ann Surg Oncol. 2009;16(8):2315–20.CrossRef Kang S, Nam BH. Does neoadjuvant chemotherapy increase optimal cytoreduction rate in advanced ovarian cancer? Meta-analysis of 21 studies. Ann Surg Oncol. 2009;16(8):2315–20.CrossRef
4.
Zurück zum Zitat Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol. 2002;20(5):1248–59.CrossRef Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol. 2002;20(5):1248–59.CrossRef
5.
Zurück zum Zitat du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer. 2009;115(6):1234–44.CrossRef du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer. 2009;115(6):1234–44.CrossRef
6.
Zurück zum Zitat Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRef Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRef
7.
Zurück zum Zitat Rustin GJ, Vergote I, Eisenhauer E, Pujade-Lauraine E, Quinn M, Thigpen T, et al. Definitions for response and progression in Ovarian Cancer Clinical Trials Incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011;21(2):419–23.CrossRef Rustin GJ, Vergote I, Eisenhauer E, Pujade-Lauraine E, Quinn M, Thigpen T, et al. Definitions for response and progression in Ovarian Cancer Clinical Trials Incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011;21(2):419–23.CrossRef
8.
Zurück zum Zitat Rodriguez N, Rauh-Hain JA, Shoni M, Berkowitz RS, Muto MG, Feltmate C, et al. Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy. Gynecol Oncol. 2012;125(2):362–6.CrossRef Rodriguez N, Rauh-Hain JA, Shoni M, Berkowitz RS, Muto MG, Feltmate C, et al. Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy. Gynecol Oncol. 2012;125(2):362–6.CrossRef
9.
Zurück zum Zitat Furukawa N, Sasaki Y, Shigemitsu A, Akasaka J, Kanayama S, Kawaguchi R, et al. CA-125 cut-off value as a predictor for complete interval debulking surgery after neoadjuvant chemotherapy in patients with advanced ovarian cancer. J Gynecol Oncol. 2013;24(2):141–5.CrossRef Furukawa N, Sasaki Y, Shigemitsu A, Akasaka J, Kanayama S, Kawaguchi R, et al. CA-125 cut-off value as a predictor for complete interval debulking surgery after neoadjuvant chemotherapy in patients with advanced ovarian cancer. J Gynecol Oncol. 2013;24(2):141–5.CrossRef
10.
Zurück zum Zitat Vasudev NS, Trigonis I, Cairns DA, Hall GD, Jackson DP, Broadhead T, et al. The prognostic and predictive value of CA-125 regression during neoadjuvant chemotherapy for advanced ovarian or primary peritoneal carcinoma. Arch Gynecol Obstet. 2011;284(1):221–7.CrossRef Vasudev NS, Trigonis I, Cairns DA, Hall GD, Jackson DP, Broadhead T, et al. The prognostic and predictive value of CA-125 regression during neoadjuvant chemotherapy for advanced ovarian or primary peritoneal carcinoma. Arch Gynecol Obstet. 2011;284(1):221–7.CrossRef
11.
Zurück zum Zitat Riedinger JM, Wafflart J, Ricolleau G, Eche N, Larbre H, Basuyau JP, et al. CA 125 half-life and CA 125 nadir during induction chemotherapy are independent predictors of epithelial ovarian cancer outcome: results of a French multicentric study. Ann Oncol. 2006;17(8):1234–8.CrossRef Riedinger JM, Wafflart J, Ricolleau G, Eche N, Larbre H, Basuyau JP, et al. CA 125 half-life and CA 125 nadir during induction chemotherapy are independent predictors of epithelial ovarian cancer outcome: results of a French multicentric study. Ann Oncol. 2006;17(8):1234–8.CrossRef
12.
Zurück zum Zitat van Altena AM, Kolwijck E, Spanjer MJ, Hendriks JC, Massuger LF, de Hullu JA. CA125 nadir concentration is an independent predictor of tumor recurrence in patients with ovarian cancer: a population based study. Gynecol Oncol. 2010;119(2):265–9.CrossRef van Altena AM, Kolwijck E, Spanjer MJ, Hendriks JC, Massuger LF, de Hullu JA. CA125 nadir concentration is an independent predictor of tumor recurrence in patients with ovarian cancer: a population based study. Gynecol Oncol. 2010;119(2):265–9.CrossRef
13.
Zurück zum Zitat Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, Verch T, et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 2008;108(2):402–8.CrossRef Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, Verch T, et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 2008;108(2):402–8.CrossRef
14.
Zurück zum Zitat Huhtinen K, Suvitie P, Hiissa J, Junnila J, Huvila J, Kujari H, et al. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer. 2009;100(8):1315–9.CrossRef Huhtinen K, Suvitie P, Hiissa J, Junnila J, Huvila J, Kujari H, et al. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer. 2009;100(8):1315–9.CrossRef
15.
Zurück zum Zitat Park Y, Lee JH, Hong DJ, Lee EY, Kim HS. Diagnostic performances of HE4 and CA125 for the detection of ovarian cancer from patients with various gynecologic and non-gynecologic diseases. Clin Biochem. 2011;44(10–11):884–8.CrossRef Park Y, Lee JH, Hong DJ, Lee EY, Kim HS. Diagnostic performances of HE4 and CA125 for the detection of ovarian cancer from patients with various gynecologic and non-gynecologic diseases. Clin Biochem. 2011;44(10–11):884–8.CrossRef
16.
Zurück zum Zitat Angioli R, Capriglione S, Aloisi A, Guzzo F, Luvero D, Miranda A, et al. Can HE4 predict platinum response during first-line chemotherapy in ovarian cancer? Tumour Biol. 2014 Apr 21. Angioli R, Capriglione S, Aloisi A, Guzzo F, Luvero D, Miranda A, et al. Can HE4 predict platinum response during first-line chemotherapy in ovarian cancer? Tumour Biol. 2014 Apr 21.
17.
Zurück zum Zitat Anastasi E, Marchei GG, Viggiani V, Gennarini G, Frati L, Reale MG. HE4: a new potential early biomarker for the recurrence of ovarian cancer. Tumour Biol. 2010;31(2):113–9.CrossRef Anastasi E, Marchei GG, Viggiani V, Gennarini G, Frati L, Reale MG. HE4: a new potential early biomarker for the recurrence of ovarian cancer. Tumour Biol. 2010;31(2):113–9.CrossRef
18.
Zurück zum Zitat Angioli R, Plotti F, Capriglione S, Aloisi A, Montera R, Luvero D, et al. Can the preoperative HE4 level predict optimal cytoreduction in patients with advanced ovarian carcinoma? Gynecol Oncol. 2013;128(3):579–83.CrossRef Angioli R, Plotti F, Capriglione S, Aloisi A, Montera R, Luvero D, et al. Can the preoperative HE4 level predict optimal cytoreduction in patients with advanced ovarian carcinoma? Gynecol Oncol. 2013;128(3):579–83.CrossRef
19.
Zurück zum Zitat Braicu EI, Fotopoulou C, Van Gorp T, Richter R, Chekerov R, Hall C, et al. Preoperative HE4 expression in plasma predicts surgical outcome in primary ovarian cancer patients: results from the OVCAD study. Gynecol Oncol. 2013;128(2):245–51.CrossRef Braicu EI, Fotopoulou C, Van Gorp T, Richter R, Chekerov R, Hall C, et al. Preoperative HE4 expression in plasma predicts surgical outcome in primary ovarian cancer patients: results from the OVCAD study. Gynecol Oncol. 2013;128(2):245–51.CrossRef
20.
Zurück zum Zitat Fagotti A, Ferrandina G, Fanfani F, Garganese G, Vizzielli G, Carone V, et al. Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma. Am J Obstet Gynecol. 2008;199:642e1–6.CrossRef Fagotti A, Ferrandina G, Fanfani F, Garganese G, Vizzielli G, Carone V, et al. Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma. Am J Obstet Gynecol. 2008;199:642e1–6.CrossRef
21.
Zurück zum Zitat Menczer J, Usviatzov I, Ben-Shem E, Golan A, Levy T. Neoadjuvant chemotherapy in ovarian, primary peritoneal and tubal carcinoma: can imaging results prior to interval debulking predict survival? J Gynecol Oncol. 2011;22(3):183–7.CrossRef Menczer J, Usviatzov I, Ben-Shem E, Golan A, Levy T. Neoadjuvant chemotherapy in ovarian, primary peritoneal and tubal carcinoma: can imaging results prior to interval debulking predict survival? J Gynecol Oncol. 2011;22(3):183–7.CrossRef
22.
23.
Zurück zum Zitat Hynninen J, Auranen A, Dean K, Lavonius M, Carpen O, Perheentupa A, et al. Serum HE4 profile during primary chemotherapy of epithelial ovarian cancer. Int J Gynecol Cancer. 2011;21(9):1573–8.CrossRef Hynninen J, Auranen A, Dean K, Lavonius M, Carpen O, Perheentupa A, et al. Serum HE4 profile during primary chemotherapy of epithelial ovarian cancer. Int J Gynecol Cancer. 2011;21(9):1573–8.CrossRef
24.
Zurück zum Zitat Yildirim Y, Ertas IE, Dogan A, Gultekin OE, Gultekin E. The predictors of response to neoadjuvant chemotherapy in advanced epithelial ovarian cancer. J Surg Oncol. 2012;105(2):200–5.CrossRef Yildirim Y, Ertas IE, Dogan A, Gultekin OE, Gultekin E. The predictors of response to neoadjuvant chemotherapy in advanced epithelial ovarian cancer. J Surg Oncol. 2012;105(2):200–5.CrossRef
25.
Zurück zum Zitat Bellati F, Gasparri ML, Caccetta J, Palaia I, Benedetti Panici P. Response criteria can be misleading when drawing conclusion regarding neoadjuvant chemotherapy in advanced ovarian cancer. J Surg Oncol. 2012;106(4):529. author reply 527-8.CrossRef Bellati F, Gasparri ML, Caccetta J, Palaia I, Benedetti Panici P. Response criteria can be misleading when drawing conclusion regarding neoadjuvant chemotherapy in advanced ovarian cancer. J Surg Oncol. 2012;106(4):529. author reply 527-8.CrossRef
26.
Zurück zum Zitat Tate S, Hirai Y, Takeshima N, Hasumi K. CA125 regression during neoadjuvant chemotherapy as an independent prognostic factor for survival in patients with advanced ovarian serous adenocarcinoma. J Gynecol Oncol. 2005;96(1):143–9.CrossRef Tate S, Hirai Y, Takeshima N, Hasumi K. CA125 regression during neoadjuvant chemotherapy as an independent prognostic factor for survival in patients with advanced ovarian serous adenocarcinoma. J Gynecol Oncol. 2005;96(1):143–9.CrossRef
27.
Zurück zum Zitat Le T, Hopkins L, Faught W, Fung-Kee-Fung M. The lack of significance of Ca125 response in epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and delayed primary surgical debulking. Gynecol Oncol. 2007;105(3):712–5.CrossRef Le T, Hopkins L, Faught W, Fung-Kee-Fung M. The lack of significance of Ca125 response in epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and delayed primary surgical debulking. Gynecol Oncol. 2007;105(3):712–5.CrossRef
Metadaten
Titel
Serum HE4 and CA125 as predictors of response and outcome during neoadjuvant chemotherapy of advanced high-grade serous ovarian cancer
verfasst von
Tuulia Vallius
Johanna Hynninen
Annika Auranen
Olli Carpén
Jaakko Matomäki
Sinikka Oksa
Johanna Virtanen
Seija Grénman
Publikationsdatum
01.12.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 12/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2553-1

Weitere Artikel der Ausgabe 12/2014

Tumor Biology 12/2014 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.