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3. Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study

Author

Casadei, Chiara, Scarpi, Emanuela, Conteduca, Vincenza, Gurioli, Giorgia, Cursano, Maria Concetta, Brighi, Nicole, Lolli, Cristian, Schepisi, Giuseppe, Basso, Umberto, Fornarini, Giuseppe, Bleve, Sara, Farolfi, Alberto, Altavilla, Amelia, Burgio, Salvatore Luca, Giunta, Emilio Francesco, Gianni, Caterina, Filograna, Alessia, Ulivi, Paola, Olmos, David, Castro, Elena, and De Giorgi, Ugo

Published
2024
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4. Plasma tumour DNA dynamics and circulating subclones patterns in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel in a prospective biomarker trial (NCT03381326).

Author

Brighi, Nicole, primary, Wetterskog, Daniel, additional, Gurioli, Giorgia, additional, Orlando, Francesco, additional, Conteduca, Vincenza, additional, Vainauskas, Osvaldas, additional, Giunta, Emilio Francesco, additional, Bleve, Sara, additional, Casadei, Chiara, additional, Cremaschi, Paolo, additional, Basso, Umberto, additional, Pierantoni, Francesco, additional, Fornarini, Giuseppe, additional, Mosca, Alessandra, additional, Nicodemo, Maurizio, additional, Banna, Giuseppe Luigi, additional, Ulivi, Paola, additional, Demichelis, Francesca, additional, De Giorgi, Ugo, additional, and Attard, Gerhardt, additional

Published
2024
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7. Circulating androgen receptor gene amplification and resistance to 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer: results of a Phase 2 trial

Author

De Giorgi, Ugo, Sansovini, Maddalena, Severi, Stefano, Nicolini, Silvia, Monti, Manuela, Gurioli, Giorgia, Foca, Flavia, Casadei, Chiara, Conteduca, Vincenza, Celli, Monica, Di Iorio, Valentina, Calistri, Daniele, Matteucci, Federica, von Eyben, Finn Edler, Attard, Gerhardt, and Paganelli, Giovanni

Published
2021
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10. Genome-wide plasma DNA methylation features of metastatic prostate cancer

Author

Wu, Anjui, Cremaschi, Paolo, Wetterskog, Daniel, Conteduca, Vincenza, Franceschini, Gian Marco, Kleftogiannis, Dimitrios, Jayaram, Anuradha, Sandhu, Shahneen, Wong, Stephen Q., Benelli, Matteo, Salvi, Samanta, Gurioli, Giorgia, Feber, Andrew, Pereira, Mariana Buongermino, Wingate, Anna Maria, Gonzalez-Billalebeita, Enrique, De Giorgi, Ugo, Demichelis, Francesca, Lise, Stefano, and Attard, Gerhardt

Subjects
Cancer treatment -- Analysis, Cancer genetics -- Care and treatment, Enzalutamide -- Analysis, Abiraterone -- Analysis, Methylation -- Analysis, DNA -- Analysis, Prostate cancer -- Care and treatment, Sulfites -- Analysis, Cancer metastasis -- Care and treatment, Genomics -- Analysis, Chemotherapy, Epithelium, Tumors, Phenotypes, Genomes, Setting (Literature), Cancer patients, Health care industry
Abstract

Tumor DNA circulates in the plasma of cancer patients admixed with DNA from noncancerous cells. The genomic landscape of plasma DNA has been characterized in metastatic castration-resistant prostate cancer (mCRPC) but the plasma methylome has not been extensively explored. Here, we performed next-generation sequencing (NGS) on plasma DNA with and without bisulfite treatment from mCRPC patients receiving either abiraterone or enzalutamide in the pre- or post-chemotherapy setting. Principal component analysis on the mCRPC plasma methylome indicated that the main contributor to methylation variance (principal component one, or PC1) was strongly correlated with genomically determined tumor fraction (r = - 0.96; P < [10.sup.8]) and characterized by hypermethylation of targets of the polycomb repressor complex 2 components. Further deconvolution of the PC1 top-correlated segments revealed that these segments are comprised of methylation patterns specific to either prostate cancer or prostate normal epithelium. To extract information specific to an individual's cancer, we then focused on an orthogonal methylation signature, which revealed enrichment for androgen receptor binding sequences and hypomethylation of these segments associated with AR copy number gain. Individuals harboring this methylation pattern had a more aggressive clinical course. Plasma methylome analysis can accurately quantitate tumor fraction and identify distinct biologically relevant mCRPC phenotypes., Introduction Analysis of plasma DNA somatic point mutations or copy number alterations through liquid biopsy has potential utility for informing treatment decisions in cancer patients with a range of tumor [...]

Published
2020
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11. Plasma tumour DNA as an early indicator of treatment response in metastatic castration-resistant prostate cancer

Author

Conteduca, Vincenza, Wetterskog, Daniel, Scarpi, Emanuela, Romanel, Alessandro, Gurioli, Giorgia, Jayaram, Anuradha, Lolli, Cristian, Tandefelt, Delila Gasi, Schepisi, Giuseppe, Casadei, Chiara, Wingate, Anna, Matteucci, Federica, Paganelli, Giovanni, Gonzalez-Billalabeitia, Enrique, Demichelis, Francesca, De Giorgi, Ugo, and Attard, Gerhardt

Published
2020
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13. Impact of the time interval between primary or interval surgery and adjuvant chemotherapy in ovarian cancer patients

Author

Farolfi, Alberto, primary, Petracci, Elisabetta, additional, Gurioli, Giorgia, additional, Tedaldi, Gianluca, additional, Casanova, Claudia, additional, Arcangeli, Valentina, additional, Amadori, Andrea, additional, Rosati, Marta, additional, Stefanetti, Marco, additional, Burgio, Salvatore Luca, additional, Cursano, Maria Concetta, additional, Lolli, Cristian, additional, Zampiga, Valentina, additional, Cangini, Ilaria, additional, Schepisi, Giuseppe, additional, and De Giorgi, Ugo, additional

Published
2023
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15. Inherited mutations in DNA damage gene repair (gDDR) in Italian men with metastatic prostate cancer.

Author

De Giorgi, Ugo, primary, Casadei, Chiara, additional, Conteduca, Vincenza, additional, Gurioli, Giorgia, additional, Scarpi, Emanuela, additional, Cursano, Maria Concetta, additional, Brighi, Nicole, additional, Lolli, Cristian, additional, Schepisi, Giuseppe, additional, Basso, Umberto, additional, Fornarini, Giuseppe, additional, Bleve, Sara, additional, Farolfi, Alberto, additional, Altavilla, Amelia, additional, Olmos, David, additional, and Castro, Elena, additional

Published
2023
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16. Serum Mass Spectrometry Proteomics and Protein Set Identification in Response to FOLFOX-4 in Drug-Resistant Ovarian Carcinoma

Author

D'Arca, D, Severi, L, Ferrari, S, Dozza, L, Marverti, G, Magni, F, Chinello, C, Pagani, L, Tagliazucchi, L, Villani, M, D'Addese, G, Piga, I, Conteduca, V, Rossi, L, Gurioli, G, De Giorgi, U, Losi, L, Costi, M, D'Arca, Domenico, Severi, Leda, Ferrari, Stefania, Dozza, Luca, Marverti, Gaetano, Magni, Fulvio, Chinello, Clizia, Pagani, Lisa, Tagliazucchi, Lorenzo, Villani, Marco, d'Addese, Gianluca, Piga, Isabella, Conteduca, Vincenza, Rossi, Lorena, Gurioli, Giorgia, De Giorgi, Ugo, Losi, Lorena, Costi, Maria Paola, D'Arca, D, Severi, L, Ferrari, S, Dozza, L, Marverti, G, Magni, F, Chinello, C, Pagani, L, Tagliazucchi, L, Villani, M, D'Addese, G, Piga, I, Conteduca, V, Rossi, L, Gurioli, G, De Giorgi, U, Losi, L, Costi, M, D'Arca, Domenico, Severi, Leda, Ferrari, Stefania, Dozza, Luca, Marverti, Gaetano, Magni, Fulvio, Chinello, Clizia, Pagani, Lisa, Tagliazucchi, Lorenzo, Villani, Marco, d'Addese, Gianluca, Piga, Isabella, Conteduca, Vincenza, Rossi, Lorena, Gurioli, Giorgia, De Giorgi, Ugo, Losi, Lorena, and Costi, Maria Paola

Abstract

Ovarian cancer is a highly lethal gynecological malignancy. Drug resistance rapidly occurs, and different therapeutic approaches are needed. So far, no biomarkers have been discovered to predict early response to therapies in the case of multi-treated ovarian cancer patients. The aim of our investigation was to identify a protein panel and the molecular pathways involved in chemotherapy response through a combination of studying proteomics and network enrichment analysis by considering a subset of samples from a clinical setting. Differential mass spectrometry studies were performed on 14 serum samples from patients with heavily pretreated platinum-resistant ovarian cancer who received the FOLFOX-4 regimen as a salvage therapy. The serum was analyzed at baseline time (T0) before FOLFOX-4 treatment, and before the second cycle of treatment (T1), with the aim of understanding if it was possible, after a first treatment cycle, to detect significant proteome changes that could be associated with patients responses to therapy. A total of 291 shared expressed proteins was identified and 12 proteins were finally selected between patients who attained partial response or no-response to chemotherapy when both response to therapy and time dependence (T0, T1) were considered in the statistical analysis. The protein panel included APOL1, GSN, GFI1, LCATL, MNA, LYVE1, ROR1, SHBG, SOD3, TEC, VPS18, and ZNF573. Using a bioinformatics network enrichment approach and metanalysis study, relationships between serum and cellular proteins were identified. An analysis of protein networks was conducted and identified at least three biological processes with functional and therapeutic significance in ovarian cancer, including lipoproteins metabolic process, structural component modulation in relation to cellular apoptosis and autophagy, and cellular oxidative stress response. Five proteins were almost independent from the network (LYVE1, ROR1, TEC, GFI1, and ZNF573). All proteins were asso

Published
2023

17. Serum Mass Spectrometry Proteomics and Protein Set Identification in Response to FOLFOX-4 in Drug-Resistant Ovarian Carcinoma

Author

D’Arca, Domenico, primary, Severi, Leda, additional, Ferrari, Stefania, additional, Dozza, Luca, additional, Marverti, Gaetano, additional, Magni, Fulvio, additional, Chinello, Clizia, additional, Pagani, Lisa, additional, Tagliazucchi, Lorenzo, additional, Villani, Marco, additional, d’Addese, Gianluca, additional, Piga, Isabella, additional, Conteduca, Vincenza, additional, Rossi, Lorena, additional, Gurioli, Giorgia, additional, De Giorgi, Ugo, additional, Losi, Lorena, additional, and Costi, Maria Paola, additional

Published
2023
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19. Clinical Impact of Next-Generation Sequencing Multi-Gene Panel Highlighting the Landscape of Germline Alterations in Ovarian Cancer Patients

Author

Gurioli, Giorgia, primary, Tedaldi, Gianluca, additional, Farolfi, Alberto, additional, Petracci, Elisabetta, additional, Casanova, Claudia, additional, Comerci, Giuseppe, additional, Danesi, Rita, additional, Arcangeli, Valentina, additional, Ravegnani, Mila, additional, Calistri, Daniele, additional, Zampiga, Valentina, additional, Cangini, Ilaria, additional, Fonzi, Eugenio, additional, Virga, Alessandra, additional, Tassinari, Davide, additional, Rosati, Marta, additional, Ulivi, Paola, additional, and De Giorgi, Ugo, additional

Published
2022
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22. High exosomal PD-L1 expression in relation to lymph node progression in metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone (abi) or enzalutamide (enza).

Author

Conteduca, Vincenza, primary, Del Re, Marzia, additional, Scarpi, Emanuela, additional, Crucitta, Stefania, additional, Gurioli, Giorgia, additional, Restante, Giuliana, additional, Cucchiara, Federico, additional, Lolli, Cristian, additional, Brighi, Nicole, additional, Schepisi, Giuseppe, additional, Casadei, Chiara, additional, Ulivi, Paola, additional, Beltran, Himisha, additional, Danesi, Romano, additional, and De Giorgi, Ugo, additional

Published
2022
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23. Baseline Plasma Tumor DNA (ctDNA) Correlates with PSA Kinetics in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide

Author

Conteduca, Vincenza, primary, Casadei, Chiara, additional, Scarpi, Emanuela, additional, Brighi, Nicole, additional, Schepisi, Giuseppe, additional, Lolli, Cristian, additional, Gurioli, Giorgia, additional, Toma, Ilaria, additional, Poti, Giulia, additional, Farolfi, Alberto, additional, and De Giorgi, Ugo, additional

Published
2022
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25. Association of changing bone metastatic (mets) patterns with dynamics of circulating tumor DNA (ctDNA) in metastatic castration-resistant prostate cancer (mCRPC).

Author

Conteduca, Vincenza, primary, Scarpi, Emanuela, additional, Rossi, Alice, additional, Ferroni, Fabio, additional, Gurioli, Giorgia, additional, Bleve, Sara, additional, Gianni, Caterina, additional, Schepisi, Giuseppe, additional, Brighi, Nicole, additional, Lolli, Cristian, additional, Cursano, Maria Concetta, additional, Virga, Alessandra, additional, Casadei, Chiara, additional, Altavilla, Amelia, additional, Farolfi, Alberto, additional, Ulivi, Paola, additional, Barone, Domenico, additional, Matteucci, Federica, additional, Paganelli, Giovanni, additional, and De Giorgi, Ugo, additional

Published
2022
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26. Additional file 1 of Circulating tumor cell gene expression and plasma AR gene copy number as biomarkers for castration-resistant prostate cancer patients treated with cabazitaxel

Author

Gurioli, Giorgia, Conteduca, Vincenza, Brighi, Nicole, Scarpi, Emanuela, Basso, Umberto, Fornarini, Giuseppe, Mosca, Alessandra, Nicodemo, Maurizio, Banna, Giuseppe Luigi, Lolli, Cristian, Schepisi, Giuseppe, Ravaglia, Giorgia, Bondi, Isabella, Ulivi, Paola, and De Giorgi, Ugo

Abstract

Additional file 1: Table S1. Correlation analysis of gene expression biomarkers; we performed an analysis to evaluate the correlation of all the biomarkers considered.

Published
2022
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27. Combining liquid biopsy and functional imaging analysis in metastatic castration‐resistant prostate cancer helps predict treatment outcome

Author

Conteduca, Vincenza, primary, Scarpi, Emanuela, additional, Caroli, Paola, additional, Lolli, Cristian, additional, Gurioli, Giorgia, additional, Brighi, Nicole, additional, Poti, Giulia, additional, Farolfi, Alberto, additional, Altavilla, Amelia, additional, Schepisi, Giuseppe, additional, Matteucci, Federica, additional, Paganelli, Giovanni, additional, and De Giorgi, Ugo, additional

Published
2021
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28. Serum Mass Spectrometry Proteomics and Protein Set Identification in Response to FOLFOX-4 in Drug-Resistant Ovarian Carcinoma.

Author

D'Arca, Domenico, Severi, Leda, Ferrari, Stefania, Dozza, Luca, Marverti, Gaetano, Magni, Fulvio, Chinello, Clizia, Pagani, Lisa, Tagliazucchi, Lorenzo, Villani, Marco, d'Addese, Gianluca, Piga, Isabella, Conteduca, Vincenza, Rossi, Lorena, Gurioli, Giorgia, De Giorgi, Ugo, Losi, Lorena, and Costi, Maria Paola

Subjects
BLOOD serum analysis, BIOMARKERS, OVARIAN tumors, BLOOD proteins, ANALYSIS of variance, CANCER chemotherapy, AUTOPHAGY, ANTINEOPLASTIC agents, APOPTOSIS, PROTEOMICS, BIOINFORMATICS, OXIDATIVE stress, MASS spectrometry, RESEARCH funding, SALVAGE therapy, DRUG resistance in cancer cells
Abstract

Simple Summary: A mass spectrometry (MS) proteomics and molecular pathway study was applied to serum samples of patients with ovarian serous carcinoma administered the FOLFOX-4 drug combination protocol, before the second cycle of therapy. This exploratory study aimed at identifying a protein panel that could be significantly modulated during two different collection time intervals and associated with patient response to therapy. The label-free differential MS proteomic analysis of 14 serum samples was conducted and identified 291 shared expressed proteins; 12 proteins resulted in being significantly associated with response to treatment and time of sample collection. The network enrichment analysis performed through STRING and other bioinformatic tools provided a metadata validation of the panel in which the identified proteins were related to resistant ovarian cancers at the molecular level. We concluded that the discovered protein panel that guided the identification of the associated molecular pathways could be further explored in a higher number of patients. Considering the lack of biomarkers that can guide the selection of further therapeutic approaches after drug resistance appearance, our study may suggest a new direction in the discovery and validation of a protein panel as biomarkers for future clinical application. Ovarian cancer is a highly lethal gynecological malignancy. Drug resistance rapidly occurs, and different therapeutic approaches are needed. So far, no biomarkers have been discovered to predict early response to therapies in the case of multi-treated ovarian cancer patients. The aim of our investigation was to identify a protein panel and the molecular pathways involved in chemotherapy response through a combination of studying proteomics and network enrichment analysis by considering a subset of samples from a clinical setting. Differential mass spectrometry studies were performed on 14 serum samples from patients with heavily pretreated platinum-resistant ovarian cancer who received the FOLFOX-4 regimen as a salvage therapy. The serum was analyzed at baseline time (T0) before FOLFOX-4 treatment, and before the second cycle of treatment (T1), with the aim of understanding if it was possible, after a first treatment cycle, to detect significant proteome changes that could be associated with patients responses to therapy. A total of 291 shared expressed proteins was identified and 12 proteins were finally selected between patients who attained partial response or no-response to chemotherapy when both response to therapy and time dependence (T0, T1) were considered in the statistical analysis. The protein panel included APOL1, GSN, GFI1, LCATL, MNA, LYVE1, ROR1, SHBG, SOD3, TEC, VPS18, and ZNF573. Using a bioinformatics network enrichment approach and metanalysis study, relationships between serum and cellular proteins were identified. An analysis of protein networks was conducted and identified at least three biological processes with functional and therapeutic significance in ovarian cancer, including lipoproteins metabolic process, structural component modulation in relation to cellular apoptosis and autophagy, and cellular oxidative stress response. Five proteins were almost independent from the network (LYVE1, ROR1, TEC, GFI1, and ZNF573). All proteins were associated with response to drug-resistant ovarian cancer resistant and were mechanistically connected to the pathways associated with cancer arrest. These results can be the basis for extending a biomarker discovery process to a clinical trial, as an early predictive tool of chemo-response to FOLFOX-4 of heavily treated ovarian cancer patients and for supporting the oncologist to continue or to interrupt the therapy. [ABSTRACT FROM AUTHOR]

Published
2023
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31. Plasma tumor DNA is associated with increased risk of venous thromboembolism in metastatic castration‐resistant cancer patients

Author

Conteduca, Vincenza, primary, Scarpi, Emanuela, additional, Wetterskog, Daniel, additional, Brighi, Nicole, additional, Ferroni, Fabio, additional, Rossi, Alice, additional, Romanel, Alessandro, additional, Gurioli, Giorgia, additional, Bleve, Sara, additional, Gianni, Caterina, additional, Schepisi, Giuseppe, additional, Lolli, Cristian, additional, Cortesi, Pietro, additional, Matteucci, Federica, additional, Barone, Domenico, additional, Paganelli, Giovanni, additional, Demichelis, Francesca, additional, Beltran, Himisha, additional, Attard, Gerhardt, additional, and De Giorgi, Ugo, additional

Published
2021
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33. Melphalan as a Promising Treatment for BRCA-Related Ovarian Carcinoma

Author

Conteduca, Vincenza, primary, Scarpi, Emanuela, additional, Farolfi, Alberto, additional, Brighi, Nicole, additional, Rossi, Lorena, additional, Gurioli, Giorgia, additional, Lolli, Cristian, additional, Schepisi, Giuseppe, additional, Bleve, Sara, additional, Gianni, Caterina, additional, Virga, Alessandra, additional, Altavilla, Amelia, additional, Burgio, Salvatore Luca, additional, Menna, Cecilia, additional, and De Giorgi, Ugo, additional

Published
2021
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34. Plasma androgen receptor and response to adapted and standard docetaxel regimen in castration-resistant prostate cancer: A multicenter biomarker study

Author

Conteduca, Vincenza, primary, Wetterskog, Daniel, additional, Castro, Elena, additional, Scarpi, Emanuela, additional, Romero-Laorden, Nuria, additional, Gurioli, Giorgia, additional, Jayaram, Anuradha, additional, Lolli, Cristian, additional, Schepisi, Giuseppe, additional, Wingate, Anna, additional, Casadei, Chiara, additional, Lozano, Rebeca, additional, Brighi, Nicole, additional, Aragón, Isabel M., additional, Marin-Aguilera, Mercedes, additional, Gonzalez-Billalabeitia, Enrique, additional, Mellado, Begoña, additional, Olmos, David, additional, Attard, Gerhardt, additional, and De Giorgi, Ugo, additional

Published
2021
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36. Association of plasma tumor DNA (ptDNA) with increased risk of venous thromboembolism (VTE) in metastatic castration resistant prostate cancer patients (mCRPC).

Author

Conteduca, Vincenza, primary, Scarpi, Emanuela, additional, Wetterskog, Daniel, additional, Ferroni, Fabio, additional, Rossi, Alice, additional, Romanel, Alessandro, additional, Gurioli, Giorgia, additional, Bleve, Sara, additional, Gianni, Caterina, additional, Brighi, Nicole, additional, Schepisi, Giuseppe, additional, Lolli, Cristian, additional, Cortesi, Pietro, additional, Barone, Domenico, additional, Demichelis, Francesca, additional, Paganelli, Giovanni, additional, Beltran, Himisha, additional, Attard, Gerhardt, additional, and De Giorgi, Ugo, additional

Published
2021
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37. Combining molecular and functional imaging in metastatic castration-resistant prostate cancer (mCRPC).

Author

Conteduca, Vincenza, primary, Scarpi, Emanuela, additional, Wetterskog, Daniel, additional, Caroli, Paola, additional, Romanel, Alessandro, additional, Lolli, Cristian, additional, Jayaram, Anuradha, additional, Gurioli, Giorgia, additional, Brighi, Nicole, additional, Poti, Giulia, additional, Wingate, Anna, additional, Schepisi, Giuseppe, additional, Matteucci, Federica, additional, Paganelli, Giovanni, additional, Demichelis, Francesca, additional, Attard, Gerhardt, additional, and De Giorgi, Ugo, additional

Published
2021
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38. Immunosenescence in Testicular Cancer Survivors: Potential Implications of Cancer Therapies and Psychological Distress

Author

De Padova, Silvia, primary, Urbini, Milena, additional, Schepisi, Giuseppe, additional, Virga, Alessandra, additional, Meggiolaro, Elena, additional, Rossi, Lorena, additional, Fabbri, Francesco, additional, Bertelli, Tatiana, additional, Ulivi, Paola, additional, Ruffilli, Federica, additional, Casadei, Chiara, additional, Gurioli, Giorgia, additional, Rosti, Giovanni, additional, Grassi, Luigi, additional, and De Giorgi, Ugo, additional

Published
2021
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39. Plasma tumor DNA is associated with increased risk of venous thromboembolism in metastatic castration‐resistant cancer patients.

Author

Conteduca, Vincenza, Scarpi, Emanuela, Wetterskog, Daniel, Brighi, Nicole, Ferroni, Fabio, Rossi, Alice, Romanel, Alessandro, Gurioli, Giorgia, Bleve, Sara, Gianni, Caterina, Schepisi, Giuseppe, Lolli, Cristian, Cortesi, Pietro, Matteucci, Federica, Barone, Domenico, Paganelli, Giovanni, Demichelis, Francesca, Beltran, Himisha, Attard, Gerhardt, and De Giorgi, Ugo

Subjects
CASTRATION-resistant prostate cancer, THROMBOEMBOLISM, PROSTATE cancer, CANCER patients, METASTASIS, ANDROGEN deprivation therapy, DNA
Abstract

Cancer is a risk factor for venous thromboembolism (VTE). Plasma tumor DNA (ptDNA) is an independent predictor of outcome in metastatic castration‐resistant prostate cancer (mCRPC). We aimed to investigate the association between ptDNA and VTE in mCRPC. This prospective biomarker study included 180 mCRPC patients treated with abiraterone and enzalutamide from April 2013 to December 2018. We excluded patients with a previous VTE history and/or ongoing anticoagulation therapy. Targeted next‐generation sequencing was performed to determine ptDNA fraction from pretreatment plasma samples. VTE risk based on survival analysis was performed using cumulative incidence function and estimating sub‐distributional hazard ratio (SHR). At a median follow‐up of 58 months (range 0.5‐111.0), we observed 21 patients who experienced VTE with a cumulative incidence at 12 months of 17.1% (95% confidence interval [CI] 10.3‐23.9). Elevated ptDNA, visceral metastasis, prior chemotherapy and lactate dehydrogenase (LDH) were significantly associated with higher VTE incidence compared to patients with no thrombosis (12‐month estimate, 18.6% vs 3.5%, P =.0003; 44.4% vs 14.8%, P =.015; 24.7% vs 4.5%, P =.006; and 30.0% vs 13.5%, P =.05, respectively). In the multivariate analysis including ptDNA level, visceral metastases, number of lesions and serum LDH, high ptDNA fraction was the only independent factor associated with the risk of thrombosis (HR 5.78, 95% CI 1.63‐20.44, P =.006). These results first suggest that baseline ptDNA fraction in mCRPC patients treated with abiraterone or enzalutamide may be associated with increased VTE risk. These patients may be followed‐up more closely for the VTE risk, and the need for a primary thromboprophylaxis should be taken into account in mCRPC with elevated ptDNA. What's new? Patients with cancer are at increased risk for venous thromboembolism (VTE). Here, the authors test the correlation between plasma tumor DNA (ptDNA) and VTE in patients with metastatic castration‐resistant prostate cancer. In prostate cancer, the concentration of ptDNA prior to treatment can predict clinical outcome. This study enrolled 180 patients who were receiving androgen deprivation therapy. The patients with high ptDNA had a greater incidence of VTE than those with low ptDNA. These results suggest that ptDNA could be a useful tool for assessing VTE risk and improving long‐term survival. [ABSTRACT FROM AUTHOR]

Published
2022
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41. Potential Application of Chimeric Antigen Receptor (CAR)-T Cell Therapy in Renal Cell Tumors

Author

Schepisi, Giuseppe, primary, Conteduca, Vincenza, additional, Casadei, Chiara, additional, Gurioli, Giorgia, additional, Rossi, Lorena, additional, Gallà, Valentina, additional, Cursano, Maria Concetta, additional, Brighi, Nicole, additional, Lolli, Cristian, additional, Menna, Cecilia, additional, Farolfi, Alberto, additional, Burgio, Salvatore Luca, additional, Altavilla, Amelia, additional, Martinelli, Giovanni, additional, and De Giorgi, Ugo, additional

Published
2020
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42. Enzalutamide for the treatment of nonmetastatic castration-resistant prostate cancer

Author

Altavilla, Amelia, primary, Casadei, Chiara, additional, Lolli, Cristian, additional, Menna, Cecilia, additional, Ravaglia, Giorgia, additional, Gurioli, Giorgia, additional, Farolfi, Alberto, additional, Brighi, Nicole, additional, Conteduca, Vincenza, additional, Burgio, Salvatore Luca, additional, Schepisi, Giuseppe, additional, Rossi, Lorena, additional, Gargiulo, Stefania, additional, Lisotti, Ivana, additional, and De Giorgi, Ugo, additional

Published
2020
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43. Olaparib as salvage treatment for advanced germ cell tumors after chemotherapy failure: Results of the open-label, single-arm, IGG-02 phase II trial.

Author

De Giorgi, Ugo, primary, Schepisi, Giuseppe, additional, Gurioli, Giorgia, additional, Pisano, Carmela, additional, Basso, Umberto, additional, Lolli, Cristian, additional, Petracci, Elisabetta, additional, Casadei, Chiara, additional, Cecere, Sabrina Chiara, additional, Attademo, Laura, additional, Clemente, Alberto, additional, Zampiga, Valentina, additional, Galla, Valentina, additional, Cangini, Ilaria, additional, Di Napoli, Marilena, additional, Valmorri, Linda, additional, and Pignata, Sandro, additional

Published
2020
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44. Use of plasma androgen receptor (AR) testing to optimize docetaxel chemotherapy in castration-resistant prostate cancer (CRPC): A multicenter biomarker study.

Author

Conteduca, Vincenza, primary, Castro, Elena, additional, Wetterskog, Daniel, additional, Scarpi, Emanuela, additional, Romero-Laorden, Nuria, additional, Gurioli, Giorgia, additional, Jayaram, Anuradha, additional, Lolli, Cristian, additional, Schepisi, Giuseppe, additional, Wingate, Anna, additional, Casadei, Chiara, additional, Lozano, Rebeca, additional, Brighi, Nicole, additional, Aragon, Isabel, additional, Marín-Aguilera, Mercedes, additional, González-Billalabeitia, Enrique, additional, Mellado, Begona, additional, Olmos, David, additional, Attard, Gerhardt, additional, and De Giorgi, Ugo, additional

Published
2020
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45. Gene expression in circulating tumor cells (CTC) and plasma androgen receptor (AR) gene copy number (CN) for castration-resistant prostate cancer (CRPC) patients (pts) treated with cabazitaxel.

Author

Gurioli, Giorgia, primary, Conteduca, Vincenza, additional, Basso, Umberto, additional, Fornarini, Giuseppe, additional, Mosca, Alessandra, additional, Nicodemo, Maurizio, additional, Banna, Giuseppe Luigi, additional, Lolli, Cristian, additional, Schepisi, Giuseppe, additional, Gargiulo, Stefania, additional, Altavilla, Amelia, additional, Testoni, Sara, additional, Scarpi, Emanuela, additional, and De Giorgi, Ugo, additional

Published
2020
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47. Multimodal Approach to Outcome Prediction in Metastatic Castration-Resistant Prostate Cancer by Integrating Functional Imaging and Plasma DNA Analysis

Author

Conteduca, Vincenza, primary, Scarpi, Emanuela, additional, Matteucci, Federica, additional, Caroli, Paola, additional, Ravaglia, Giorgia, additional, Fantini, Lorenzo, additional, Gurioli, Giorgia, additional, Schepisi, Giuseppe, additional, Wetterskog, Daniel, additional, Menna, Cecilia, additional, Burgio, Salvatore Luca, additional, Lolli, Cristian, additional, Paganelli, Giovanni, additional, Attard, Gerhardt, additional, and De Giorgi, Ugo, additional

Published
2019
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48. Plasma Androgen Receptor in Prostate Cancer

Author

Conteduca, Vincenza, primary, Gurioli, Giorgia, additional, Brighi, Nicole, additional, Lolli, Cristian, additional, Schepisi, Giuseppe, additional, Casadei, Chiara, additional, Burgio, Salvatore Luca, additional, Gargiulo, Stefania, additional, Ravaglia, Giorgia, additional, Rossi, Lorena, additional, Altavilla, Amelia, additional, Farolfi, Alberto, additional, Menna, Cecilia, additional, Colangione, Sarah Pia, additional, Pulvirenti, Mario, additional, Romeo, Antonino, additional, and De Giorgi, Ugo, additional

Published
2019
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49. Combining liquid biopsy and functional imaging analysis in metastatic castration‐resistant prostate cancer helps predict treatment outcome.

Author

Conteduca, Vincenza, Scarpi, Emanuela, Caroli, Paola, Lolli, Cristian, Gurioli, Giorgia, Brighi, Nicole, Poti, Giulia, Farolfi, Alberto, Altavilla, Amelia, Schepisi, Giuseppe, Matteucci, Federica, Paganelli, Giovanni, and De Giorgi, Ugo

Abstract

Plasma tumour DNA (ptDNA) is a potential early noninvasive biomarker of treatment outcome in metastatic castration‐resistant prostate cancer (mCRPC). Herein, we investigated whether pretreatment ptDNA levels reflect metabolic tumour burden in mCRPC and better predict treatment outcome in combination with functional imaging. Targeted next‐generation sequencing was performed to estimate the ptDNA fraction from 102 mCRPC patients receiving abiraterone or enzalutamide. The maximum standardized uptake value (SUVmax), total lesion activity (TLA) and metabolic tumour volume (MTV) were evaluated on 18F‐fluorocholine positron emission tomography/computed tomography. We assessed a Weibull multiple regression model to determine the combined impact of clinical, molecular and imaging characteristics on overall survival (OS) and progression‐free survival (PFS), and to obtain prognostic scores. A significant association was seen between ptDNA and SUVmax, MTV and TLA. For survival analysis, patients were randomly allocated into a training (n = 68) and a validation (n = 34) set. In the training set, multivariable analyses showed that ptDNA, MTV and serum lactate dehydrogenase together with visceral metastasis were independent predictors of both OS and PFS. Prognostic scores were generated, with the identification of three groups of patients with significantly different median OS (29.2, 15.9 and 8.7 months) and PFS (13.3, 7.7 and 3.2 months) probabilities. The differences in median survival between risk groups were confirmed in the validation cohort for both OS and PFS. In our study, we showed that integrating plasma DNA analysis with functional imaging may improve prognostic risk stratification and treatment selection in mCRPC. [ABSTRACT FROM AUTHOR]

Published
2022
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50. Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer

Author

Conteduca, Vincenza, Jayaram, Anuradha, Romero-Laorden, Nuria, Wetterskog, Daniel, Salvi, Samanta, Gurioli, Giorgia, Morales Barrera, Rafael, Institut Català de la Salut, [Conteduca V] Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK. [Jayaram A] Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK. The Royal Marsden NHS Foundation Trust, London, UK. University College London Cancer Institute, London, UK. [Romero-Laorden N] Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre, Madrid, Spain. Hospital Universitario La Princesa, Madrid, Spain. [Wetterskog D] Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK. University College London Cancer Institute, London, UK. [Salvi S, Gurioli G] Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. [Morales R] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, and Hospital Universitari Vall d'Hebron

Subjects
Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Alicyclic::Cycloparaffins::Cyclodecanes::Taxoids::Docetaxel [CHEMICALS AND DRUGS], hormonas, sustitutos de hormonas y antagonistas de hormonas::antagonistas de hormonas::antagonistas de andrógenos [COMPUESTOS QUÍMICOS Y DROGAS], Pròstata - Càncer, Metàstasi, compuestos orgánicos::hidrocarburos::hidrocarburos cíclicos::hidrocarburos alicíclicos::cicloparafinas::ciclodecanos::taxoides::docetaxel [COMPUESTOS QUÍMICOS Y DROGAS], neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración [ENFERMEDADES], Hormones, Hormone Substitutes, and Hormone Antagonists::Hormone Antagonists::Androgen Antagonists::Androgen Receptor Antagonists [CHEMICALS AND DRUGS], Antiandrògens, Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms::Prostatic Neoplasms, Castration-Resistant [DISEASES]
Abstract

Càncer de pròstata; Receptor d'andrògens; Docetaxel Cáncer de próstata; Receptor de andrógenos; Docetaxel Prostate cancer; Androgen receptor; Docetaxel Plasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide, but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform an exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institutional study was a pooled analysis of AR status, determined by droplet digital polymerase chain reaction, on pretreatment plasma samples. We evaluated associations between plasma AR and overall/progression-free survival (OS/PFS) and prostate-specific antigen (PSA) response rate in 163 docetaxel-treated patients. OS was significantly shorter in case of AR gain (hazard ratio [HR]=1.61, 95% confidence interval [CI]=1.08-2.39, p=0.018), but not PFS (HR=1.04, 95% CI 0.74-1.46, p=0.8) or PSA response (odds ratio=1.14, 95% CI=0.65-1.99, p=0.7). We investigated the interaction between plasma AR and treatment type after incorporating updated data from our prior study of 73 chemotherapy-naïve, abiraterone/enzalutamide-treated patients, with data from 115 first-line docetaxel patients. In an exploratory analysis of mCRPC patients receiving first-line therapies, a significant interaction was observed between plasma AR and docetaxel versus abiraterone/enzalutamide for OS (HR=0.16, 95% CI=0.06-0.46, p

Published
2019

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