Ricardo Leão1, Ton van Agthoven2, Arnaldo Figueiredo3, Michael A S Jewett4, Kamel Fadaak4, Joan Sweet5, Ardalan E Ahmad4, Lynn Anson-Cartwright4, Peter Chung6, Aaron Hansen7, Padraig Warde6, Pedro Castelo-Branco8, Martin O'Malley9, Philippe L Bedard10, Leendert H J Looijenga11, Robert J Hamilton12. 1. Department of Surgery (Urology) and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Faculty of Medicine, University of Coimbra, Coimbra, Portugal. 2. Department of Pathology, Laboratory for Experimental Patho-Oncology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands. 3. Faculty of Medicine, University of Coimbra, Coimbra, Portugal. 4. Department of Surgery (Urology) and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. 5. Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. 6. Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. 7. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 8. Centre for Biomedical Research (CBMR), University of Algarve, Faro, Portugal. 9. Department of Medical Imaging, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. 10. Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 11. Department of Pathology, Laboratory for Experimental Patho-Oncology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: l.looijenga@erasmusmc.nl. 12. Department of Surgery (Urology) and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Electronic address: rob.hamilton@uhn.ca.
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.
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.
Authors: John T Lafin; Matthew J Murray; Nicholas Coleman; A Lindsay Frazier; James F Amatruda; Aditya Bagrodia Journal: Mol Diagn Ther Date: 2021-04-24 Impact factor: 4.074
Authors: John T Lafin; Nirmish Singla; Solomon L Woldu; Yair Lotan; Cheryl M Lewis; Kuntal Majmudar; Anna Savelyeva; Payal Kapur; Vitaly Margulis; Douglas W Strand; Matthew J Murray; James F Amatruda; Aditya Bagrodia Journal: Eur Urol Date: 2019-11-05 Impact factor: 20.096
Authors: Mette Pernille Myklebust; Anne Mette Søviknes; Ole Johan Halvorsen; Anna Thor; Olav Dahl; Helge Ræder Journal: Cancer Genomics Proteomics Date: 2022 Mar-Apr Impact factor: 4.069
Authors: Liang Cheng; Peter Albers; Daniel M Berney; Darren R Feldman; Gedske Daugaard; Timothy Gilligan; Leendert H J Looijenga Journal: Nat Rev Dis Primers Date: 2018-10-05 Impact factor: 52.329
Authors: Bettina Baessler; Tim Nestler; Daniel Pinto Dos Santos; Pia Paffenholz; Vikram Zeuch; David Pfister; David Maintz; Axel Heidenreich Journal: Eur Radiol Date: 2019-12-11 Impact factor: 5.315
Authors: Lara Kremer; Melanie von Brandenstein; Maike Wittersheim; Barbara Koeditz; Pia Paffenholz; Martin Hellmich; David Pfister; Axel Heidenreich; Tim Nestler Journal: Transl Androl Urol Date: 2021-04
Authors: John T Lafin; Alexander P Kenigsberg; Xiaosong Meng; Dreaux Abe; Anna Savelyeva; Nirmish Singla; Solomon L Woldu; Yair Lotan; Ryan J Mauck; Cheryl M Lewis; Vitaly Margulis; Daniel Wong; Liwei Jia; Payal Kapur; Lin Xu; Ryan W Speir; Gregory T Chesnut; A Lindsay Frazier; Douglas W Strand; Nicholas Coleman; Matthew J Murray; James F Amatruda; Aditya Bagrodia Journal: Eur Urol Open Sci Date: 2021-03-05