Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor

Ricardo Leão; Ton van Agthoven; Arnaldo Figueiredo; Michael A.S. Jewett; Kamel Fadaak; Joan Sweet; Ardalan E. Ahmad; Lynn Anson-Cartwright; Peter Chung; Aaron Hansen; Padraig Warde; Pedro Castelo-Branco; Martin O'Malley; Philippe L. Bedard; Leendert H.J. Looijenga; Robert J. Hamilton

doi:10.1016/j.juro.2018.02.068

Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor

Ricardo Leão, Ton van Agthoven, Arnaldo Figueiredo, Michael A.S. Jewett, Kamel Fadaak, Joan Sweet, Ardalan E. Ahmad, Lynn Anson-Cartwright, Peter Chung, Aaron Hansen, Padraig Warde, Pedro Castelo-Branco, Martin O'Malley, Philippe L. Bedard, Leendert H.J. Looijenga, Robert J. Hamilton

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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PURPOSE: Retroperitoneal lymph node dissection is recommended for residual masses greater than 1 cm after chemotherapy of nonseminomatous germ cell tumors. Currently there is no reliable predictor of post-chemotherapy retroperitoneal lymph node dissection histology. Up to 50% of patients harbor necrosis/fibrosis only so that a potentially morbid surgery has limited therapeutic value. In this study we evaluated the ability of defined serum miRNAs to predict residual viable nonseminomatous germ cell tumors after chemotherapy.

MATERIALS AND METHODS: Levels of serum miRNA, including miR-371a-3p, miR-373-3p and miR-367-3p, were measured using the ampTSmiR (amplification targeted serum miRNA) test in 82 patients, including 39 in cohort 1 and 43 in cohort 2, who were treated with orchiectomy, chemotherapy and post-chemotherapy retroperitoneal lymph node dissection. miRNA levels were compared to clinical characteristics and serum tumor markers, and correlated with the presence of viable germ cell tumor vs fibrosis/necrosis and teratoma. ROC analysis was done to determine miRNA discriminative capacity.

RESULTS: miRNA levels were significantly associated with disease extent at chemotherapy and they decreased significantly after chemotherapy. Conventional serum tumor marker levels were uninformative after chemotherapy. However, after chemotherapy miRNA levels remained elevated in patients harboring viable germ cell tumor in post-chemotherapy retroperitoneal lymph node dissection specimens. miR-371a-3p demonstrated the highest discriminative capacity for viable germ cell tumors (AUC 0.874, 95% CI 0.774-0.974, p <0.0001). Using an adapted hypothetical cutoff of 3 cm or less for surgical intervention miR-371a-3p correctly stratified all patients with viable residual retroperitoneal germ cell tumors with 100% sensitivity (p = 0.02).

CONCLUSIONS: Our study demonstrates for the first time the potential value of miR-371a-3p to predict viable germ cell tumors in residual masses after chemotherapy. Prospective studies are required to confirm clinical usefulness.

Originele taal-2	Engels
Pagina's (van-tot)	126-135
Aantal pagina's	10
Tijdschrift	Journal of Urology
Volume	200
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1016/j.juro.2018.02.068
Status	Gepubliceerd - jul. 2018
Extern gepubliceerd	Ja

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10.1016/j.juro.2018.02.068

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Leão, R., van Agthoven, T., Figueiredo, A., Jewett, M. A. S., Fadaak, K., Sweet, J., Ahmad, A. E., Anson-Cartwright, L., Chung, P., Hansen, A., Warde, P., Castelo-Branco, P., O'Malley, M., Bedard, P. L., Looijenga, L. H. J., & Hamilton, R. J. (2018). Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor. Journal of Urology, 200(1), 126-135. https://doi.org/10.1016/j.juro.2018.02.068

@article{0723e685403a4582a6addc1de0881a93,

title = "Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor",

abstract = "PURPOSE: Retroperitoneal lymph node dissection is recommended for residual masses greater than 1 cm after chemotherapy of nonseminomatous germ cell tumors. Currently there is no reliable predictor of post-chemotherapy retroperitoneal lymph node dissection histology. Up to 50% of patients harbor necrosis/fibrosis only so that a potentially morbid surgery has limited therapeutic value. In this study we evaluated the ability of defined serum miRNAs to predict residual viable nonseminomatous germ cell tumors after chemotherapy.MATERIALS AND METHODS: Levels of serum miRNA, including miR-371a-3p, miR-373-3p and miR-367-3p, were measured using the ampTSmiR (amplification targeted serum miRNA) test in 82 patients, including 39 in cohort 1 and 43 in cohort 2, who were treated with orchiectomy, chemotherapy and post-chemotherapy retroperitoneal lymph node dissection. miRNA levels were compared to clinical characteristics and serum tumor markers, and correlated with the presence of viable germ cell tumor vs fibrosis/necrosis and teratoma. ROC analysis was done to determine miRNA discriminative capacity.RESULTS: miRNA levels were significantly associated with disease extent at chemotherapy and they decreased significantly after chemotherapy. Conventional serum tumor marker levels were uninformative after chemotherapy. However, after chemotherapy miRNA levels remained elevated in patients harboring viable germ cell tumor in post-chemotherapy retroperitoneal lymph node dissection specimens. miR-371a-3p demonstrated the highest discriminative capacity for viable germ cell tumors (AUC 0.874, 95% CI 0.774-0.974, p <0.0001). Using an adapted hypothetical cutoff of 3 cm or less for surgical intervention miR-371a-3p correctly stratified all patients with viable residual retroperitoneal germ cell tumors with 100% sensitivity (p = 0.02).CONCLUSIONS: Our study demonstrates for the first time the potential value of miR-371a-3p to predict viable germ cell tumors in residual masses after chemotherapy. Prospective studies are required to confirm clinical usefulness.",

keywords = "diagnosis, germ cell and embryonal, microRNAs, neoplasm, neoplasms, residual, testis",

author = "Ricardo Le{\~a}o and {van Agthoven}, Ton and Arnaldo Figueiredo and Jewett, {Michael A.S.} and Kamel Fadaak and Joan Sweet and Ahmad, {Ardalan E.} and Lynn Anson-Cartwright and Peter Chung and Aaron Hansen and Padraig Warde and Pedro Castelo-Branco and Martin O'Malley and Bedard, {Philippe L.} and Looijenga, {Leendert H.J.} and Hamilton, {Robert J.}",

note = "Publisher Copyright: {\textcopyright} 2018 American Urological Association Education and Research, Inc.",

year = "2018",

month = jul,

doi = "10.1016/j.juro.2018.02.068",

language = "English",

volume = "200",

pages = "126--135",

journal = "Journal of Urology",

issn = "0022-5347",

publisher = "Elsevier Inc.",

number = "1",

}

Leão, R, van Agthoven, T, Figueiredo, A, Jewett, MAS, Fadaak, K, Sweet, J, Ahmad, AE, Anson-Cartwright, L, Chung, P, Hansen, A, Warde, P, Castelo-Branco, P, O'Malley, M, Bedard, PL, Looijenga, LHJ & Hamilton, RJ 2018, 'Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor', Journal of Urology, vol. 200, nr. 1, blz. 126-135. https://doi.org/10.1016/j.juro.2018.02.068

TY - JOUR

T1 - Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor

AU - Leão, Ricardo

AU - van Agthoven, Ton

AU - Figueiredo, Arnaldo

AU - Jewett, Michael A.S.

AU - Fadaak, Kamel

AU - Sweet, Joan

AU - Ahmad, Ardalan E.

AU - Anson-Cartwright, Lynn

AU - Chung, Peter

AU - Hansen, Aaron

AU - Warde, Padraig

AU - Castelo-Branco, Pedro

AU - O'Malley, Martin

AU - Bedard, Philippe L.

AU - Looijenga, Leendert H.J.

AU - Hamilton, Robert J.

PY - 2018/7

Y1 - 2018/7

N2 - PURPOSE: Retroperitoneal lymph node dissection is recommended for residual masses greater than 1 cm after chemotherapy of nonseminomatous germ cell tumors. Currently there is no reliable predictor of post-chemotherapy retroperitoneal lymph node dissection histology. Up to 50% of patients harbor necrosis/fibrosis only so that a potentially morbid surgery has limited therapeutic value. In this study we evaluated the ability of defined serum miRNAs to predict residual viable nonseminomatous germ cell tumors after chemotherapy.MATERIALS AND METHODS: Levels of serum miRNA, including miR-371a-3p, miR-373-3p and miR-367-3p, were measured using the ampTSmiR (amplification targeted serum miRNA) test in 82 patients, including 39 in cohort 1 and 43 in cohort 2, who were treated with orchiectomy, chemotherapy and post-chemotherapy retroperitoneal lymph node dissection. miRNA levels were compared to clinical characteristics and serum tumor markers, and correlated with the presence of viable germ cell tumor vs fibrosis/necrosis and teratoma. ROC analysis was done to determine miRNA discriminative capacity.RESULTS: miRNA levels were significantly associated with disease extent at chemotherapy and they decreased significantly after chemotherapy. Conventional serum tumor marker levels were uninformative after chemotherapy. However, after chemotherapy miRNA levels remained elevated in patients harboring viable germ cell tumor in post-chemotherapy retroperitoneal lymph node dissection specimens. miR-371a-3p demonstrated the highest discriminative capacity for viable germ cell tumors (AUC 0.874, 95% CI 0.774-0.974, p <0.0001). Using an adapted hypothetical cutoff of 3 cm or less for surgical intervention miR-371a-3p correctly stratified all patients with viable residual retroperitoneal germ cell tumors with 100% sensitivity (p = 0.02).CONCLUSIONS: Our study demonstrates for the first time the potential value of miR-371a-3p to predict viable germ cell tumors in residual masses after chemotherapy. Prospective studies are required to confirm clinical usefulness.

AB - PURPOSE: Retroperitoneal lymph node dissection is recommended for residual masses greater than 1 cm after chemotherapy of nonseminomatous germ cell tumors. Currently there is no reliable predictor of post-chemotherapy retroperitoneal lymph node dissection histology. Up to 50% of patients harbor necrosis/fibrosis only so that a potentially morbid surgery has limited therapeutic value. In this study we evaluated the ability of defined serum miRNAs to predict residual viable nonseminomatous germ cell tumors after chemotherapy.MATERIALS AND METHODS: Levels of serum miRNA, including miR-371a-3p, miR-373-3p and miR-367-3p, were measured using the ampTSmiR (amplification targeted serum miRNA) test in 82 patients, including 39 in cohort 1 and 43 in cohort 2, who were treated with orchiectomy, chemotherapy and post-chemotherapy retroperitoneal lymph node dissection. miRNA levels were compared to clinical characteristics and serum tumor markers, and correlated with the presence of viable germ cell tumor vs fibrosis/necrosis and teratoma. ROC analysis was done to determine miRNA discriminative capacity.RESULTS: miRNA levels were significantly associated with disease extent at chemotherapy and they decreased significantly after chemotherapy. Conventional serum tumor marker levels were uninformative after chemotherapy. However, after chemotherapy miRNA levels remained elevated in patients harboring viable germ cell tumor in post-chemotherapy retroperitoneal lymph node dissection specimens. miR-371a-3p demonstrated the highest discriminative capacity for viable germ cell tumors (AUC 0.874, 95% CI 0.774-0.974, p <0.0001). Using an adapted hypothetical cutoff of 3 cm or less for surgical intervention miR-371a-3p correctly stratified all patients with viable residual retroperitoneal germ cell tumors with 100% sensitivity (p = 0.02).CONCLUSIONS: Our study demonstrates for the first time the potential value of miR-371a-3p to predict viable germ cell tumors in residual masses after chemotherapy. Prospective studies are required to confirm clinical usefulness.

KW - diagnosis

KW - germ cell and embryonal

KW - microRNAs

KW - neoplasm

KW - neoplasms

KW - residual

KW - testis

UR - http://www.scopus.com/inward/record.url?scp=85044591680&partnerID=8YFLogxK

U2 - 10.1016/j.juro.2018.02.068

DO - 10.1016/j.juro.2018.02.068

M3 - Article

C2 - 29474847

SN - 0022-5347

VL - 200

SP - 126

EP - 135

JO - Journal of Urology

JF - Journal of Urology

IS - 1

ER -

Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor

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