Giuseppe Schepisi
@irst.emr.it
Oncology Unit
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l.
Scopus Publications
Scopus Publications
Vincenza Conteduca, Piergiorgio Di Tullio, Rossana Allamprese, Giuseppina Bruno, Cristian Lolli, Giuseppe Schepisi, Aldo Rosano, Guido Giordano, Marianna Garofoli, Vincenzo Emanuele Chiuri,et al.
Springer Science and Business Media LLC
Milena Urbini, Sara Bleve, Giuseppe Schepisi, Cecilia Menna, Giorgia Gurioli, Caterina Gianni, and Ugo De Giorgi
MDPI AG
The outcome of metastatic testicular germ cell tumor patients has been dramatically improved by cisplatin-based chemotherapy combinations. However, up to 30% of patients with advanced disease relapse after first-line therapy and require salvage regimens, which include treatments with conventional-dose chemotherapy or high-dose chemotherapy with autologous stem cell transplantation. For these patients, prognosis estimation represents an essential step in the choice of medical treatment but still remains a complex challenge. The available histological, clinical, and biochemical parameters attempt to define the prognosis, but they do not reflect the tumor’s molecular and pathological features and do not predict who will exhibit resistance to the several treatments. Molecular selection of patients and validated biomarkers are highly needed in order to improve current risk stratification and identify novel therapeutic approaches for patients with recurrent disease. Biomolecular biomarkers, including microRNAs, gene expression profiles, and immune-related biomarkers are currently under investigation in testicular germ cell tumors and could potentially hold a prominent place in the future treatment selection and prognostication of these tumors. The aim of this review is to summarize current scientific data regarding prognostic and predictive biomarkers for salvage therapy in testicular germ cell tumors.
N. Brighi, V. Conteduca, G. Gurioli, E. Scarpi, M.C. Cursano, S. Bleve, C. Lolli, G. Schepisi, C. Casadei, C. Gianni,et al.
Elsevier BV
Vincenza Conteduca, Nicole Brighi, Giuseppe Schepisi, and Ugo De Giorgi
Springer Science and Business Media LLC
Giuseppe Schepisi, Caterina Gianni, Michela Palleschi, Sara Bleve, Chiara Casadei, Cristian Lolli, Laura Ridolfi, Giovanni Martinelli, and Ugo De Giorgi
MDPI AG
Breast cancer represents one of the most common tumor histologies. To date, based on the specific histotype, different therapeutic strategies, including immunotherapies, capable of prolonging survival are used. More recently, the astonishing results that were obtained from CAR-T cell therapy in haematological neoplasms led to the application of this new therapeutic strategy in solid tumors as well. Our article will deal with chimeric antigen receptor-based immunotherapy (CAR-T cell and CAR-M therapy) in breast cancer.
Alberto Farolfi, Elisabetta Petracci, Giorgia Gurioli, Gianluca Tedaldi, Claudia Casanova, Valentina Arcangeli, Andrea Amadori, Marta Rosati, Marco Stefanetti, Salvatore Luca Burgio,et al.
Frontiers Media SA
IntroductionPrimary debulking surgery (PDS), interval debulking surgery (IDS), and platinum-based chemotherapy are the current standard treatments for advanced ovarian cancer (OC). The time to initiation of adjuvant chemotherapy (TTC) could influence patient outcomes.MethodsWe conducted a multicenter retrospective cohort study of advanced (International Federation of Gynecology and Obstetrics (FIGO) stage III or IV) OC treated between 2014 and 2018 to assess progression-free survival (PFS) and overall survival (OS) in relation to TTC. All patients underwent a germline multigene panel for BRCA1/2 evaluation.ResultsAmong the 83 patients who underwent PDS, a TTC ≥ 60 days was associated with a shorter PFS (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.04–3.93, p = 0.038), although this association lost statistical significance when adjusting for residual disease (HR 1.52, 95% CI 0.75–3.06, p = 0.244, for TTC and HR 2.73, 95% CI 1.50–4.96, p = 0.001, for residual disease). Among 52 IDS patients, we found no evidence of an association between TTC and clinical outcomes. Ascites, type of chemotherapy, or germline BRCA1/2 mutational status did not influence TTC and were not associated with clinical outcomes in PDS or IDS patients.DiscussionIn conclusion, longer TTC seems to negatively affect prognosis in patients undergoing PDS, especially those with residual disease.
Giuseppe Schepisi, Caterina Gianni, Maria Concetta Cursano, Valentina Gallà, Cecilia Menna, Chiara Casadei, Sara Bleve, Cristian Lolli, Giovanni Martinelli, Giovanni Rosti,et al.
Frontiers Media SA
Germ cell tumors (GCTs) represent a heterogeneous neoplasm family affecting gonads and rarely occurring in extragonadal areas. Most of patients have a good prognosis, often even in the presence of metastatic disease; however, in almost 15% of cases, tumor relapse and platinum resistance are the main challenges. Thus, novel treatment strategies with both improved antineoplastic activity and minor treatment-related adverse events compared with platinum are really expected. In this context, the development and the high activity demonstrated by immune checkpoint inhibitors in solid tumors and, subsequently, the interesting results obtained from the use of chimeric antigen receptor (CAR-) T cell therapy in hematological tumors, have stimulated research in this direction also in GCTs. In this article, we will analyze the molecular mechanisms underlying the immune action in the development of GCTs, and we will report the data from the studies that tested the new immunotherapeutic approaches in these neoplasms.
Giorgia Gurioli, Vincenza Conteduca, Nicole Brighi, Emanuela Scarpi, Umberto Basso, Giuseppe Fornarini, Alessandra Mosca, Maurizio Nicodemo, Giuseppe Luigi Banna, Cristian Lolli,et al.
Springer Science and Business Media LLC
Abstract Background Cabazitaxel improves overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients progressing after docetaxel. In this prospective study, we evaluated the prognostic role of CTC gene expression on cabazitaxel-treated patients and its association with plasma androgen receptor (AR) copy number (CN). Methods Patients receiving cabazitaxel 20 or 25 mg/sqm for mCRPC were enrolled. Digital PCR was performed to assess plasma AR CN status. CTC enrichment was assessed using the AdnaTest EMT-2/StemCell kit. CTC expression analyses were performed for 17 genes. Data are expressed as hazard ratio (HR) or odds ratio (OR) and 95% CI. Results Seventy-four patients were fully evaluable. CTC expression of AR-V7 (HR=2.52, 1.24–5.12, p=0.011), AKR1C3 (HR=2.01, 1.06–3.81, p=0.031), AR (HR=2.70, 1.46–5.01, p=0.002), EPCAM (HR=3.75, 2.10–6.71, p< 0.0001), PSMA (HR=2.09, 1.19–3.66, p=0.01), MDK (HR=3.35, 1.83–6.13, p< 0.0001), and HPRT1 (HR=2.46, 1.44–4.18, p=0.0009) was significantly associated with OS. ALDH1 (OR=5.50, 0.97–31.22, p=0.05), AR (OR=8.71, 2.32–32.25, p=0.001), EPCAM (OR=7.26, 1.47–35.73, p=0.015), PSMA (OR=3.86, 1.10–13.50, p=0.035), MDK (OR=6.84, 1.87–24.98, p=0.004), and HPRT1 (OR=7.41, 1.82–30.19, p=0.005) expression was associated with early PD. AR CN status was significantly correlated with AR-V7 (p=0.05), EPCAM (p=0.02), and MDK (p=0.002) expression. In multivariable model, EPCAM and HPRT1 CTC expression, plasma AR CN gain, ECOG PS=2, and liver metastases and PSA were independently associated with poorer OS. In patients treated with cabazitaxel 20 mg/sqm, median OS was shorter in AR-V7 positive than negative patients (6.6 versus 14 months, HR=3.46, 1.47–8.17], p=0.004). Conclusions Baseline CTC biomarkers may be prognosticators for cabazitaxel-treated mCRPC patients. Cabazitaxel at lower (20 mg/sqm) dose was associated with poorer outcomes in AR-V7 positive patients compared to AR-V7 negative patients in a post hoc subgroup analysis. Trial registration Clinicaltrials.govNCT03381326. Retrospectively registered on 18 December 2017.
Caterina Gianni, Michela Palleschi, Giuseppe Schepisi, Chiara Casadei, Sara Bleve, Filippo Merloni, Marianna Sirico, Samanta Sarti, Lorenzo Cecconetto, Giandomenico Di Menna,et al.
Frontiers Media SA
Adaptive and innate immune cells play a crucial role as regulators of cancer development.Inflammatory cells in blood flow seem to be involved in pro-tumor activities and contribute to breast cancer progression. Circulating lymphocyte ratios such as the platelet-lymphocytes ratio (PLR), the monocyte-lymphocyte ratio (MLR) and the neutrophil-lymphocyte ratio (NLR) are new reproducible, routinely feasible and cheap biomarkers of immune response. These indexes have been correlated to prognosis in many solid tumors and there is growing evidence on their clinical applicability as independent prognostic markers also for breast cancer.In this review we give an overview of the possible value of lymphocytic indexes in advanced breast cancer prognosis and prediction of outcome. Furthermore, targeting the immune system appear to be a promising therapeutic strategy for breast cancer, especially macrophage-targeted therapies. Herein we present an overview of the ongoing clinical trials testing systemic inflammatory cells as therapeutic targets in breast cancer.
Sara Bleve, Maria Concetta Cursano, Chiara Casadei, Giuseppe Schepisi, Cecilia Menna, Milena Urbini, Caterina Gianni, Silvia De Padova, Alessia Filograna, Valentina Gallà,et al.
Frontiers Media SA
Germ cell tumors are the most common malignant tumors in male young adults. Platinum-based chemotherapy has dramatically improved the outcome of metastatic germ cell tumor patients and overall cure rates now exceed 80%. The choice of medical treatment can be guided by the prognosis estimation which is an important step during the decision-making process. IGCCCG classification plays a pivotal role in the management of advanced disease. However, histological and clinical parameters are the available factors that condition the prognosis, but they do not reflect the tumor’s molecular and pathological features and do not predict who will respond to chemotherapy. After first-line chemotherapy 20%-30% of patients relapse and for these patients, the issue of prognostic factors is far more complex. Validated biomarkers and a molecular selection of patients that reflect the pathogenesis are highly needed. The association between cancer-related systemic inflammation, tumorigenesis, and cancer progression has been demonstrated. In the last years, several studies have shown the prognostic utility of immune-inflammation indexes in different tumor types. This review analyzed the prognostic impact of inflammatory markers retrieved from routine blood draws in GCT patients.
Vincenza Conteduca, Chiara Casadei, Emanuela Scarpi, Nicole Brighi, Giuseppe Schepisi, Cristian Lolli, Giorgia Gurioli, Ilaria Toma, Giulia Poti, Alberto Farolfi,et al.
MDPI AG
Background: Baseline high circulating tumor DNA (ctDNA) fraction in plasma and androgen receptor (AR) copy number (CN) gain identify mCRPC patients with worse outcomes. This study aimed to assess if ctDNA associates with PSA kinetics. Methods: In this prospective biomarker study, we evaluate ctDNA fraction and AR CN from plasma samples. We divided patients into high and low ctDNA level and in AR gain and AR normal. Results: 220 baseline samples were collected from mCRPC treated with abiraterone (n = 140) or enzalutamide (n = 80). A lower rate of PSA decline ≥ 50% was observed in patients with high ctDNA (p = 0.017) and AR gain (p = 0.0003). Combining ctDNA fraction and AR CN, we found a different median PSA progression-free survival (PFS) among four groups: (1) low ctDNA/AR normal, (2) high ctDNA/AR normal, (3) low ctDNA/AR gain, and (4) high ctDNA/AR gain (11.4 vs. 5.0 vs. 4.8 vs. 3.7 months, p < 0.0001). In a multivariable analysis, high ctDNA, AR gain, PSA DT, PSA DT velocity remained independent predictors of PSA PFS. Conclusions: Elevated ctDNA levels and AR gain are negatively and independently correlated with PSA kinetics in mCRPC men treated with abiraterone or enzalutamide.
Vincenza Conteduca, Emanuela Scarpi, Daniel Wetterskog, Nicole Brighi, Fabio Ferroni, Alice Rossi, Alessandro Romanel, Giorgia Gurioli, Sara Bleve, Caterina Gianni,et al.
Wiley
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.
Vincenza Conteduca, Emanuela Scarpi, Paola Caroli, Cristian Lolli, Giorgia Gurioli, Nicole Brighi, Giulia Poti, Alberto Farolfi, Amelia Altavilla, Giuseppe Schepisi,et al.
Wiley
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.
Milena Urbini, Giuseppe Schepisi, Sara Bleve, Alessandra Virga, Caterina Gianni, Giorgia Gurioli, Paola Ulivi, and Ugo De Giorgi
MDPI AG
Mediastinal germ cell tumors (MGCTs) share histologic, molecular and biomarkers features with testicular GCTs; however, nonseminomatous MGCTs are usually more aggressive and have poorer prognosis than nonseminomatous TGCTs. Most nonseminomatous MGCT cases show early resistance to platinum-based therapies and seldom have been associated with the onset of one or more concomitant somatic malignancies, in particular myeloid neoplasms with recent findings supporting a common, shared genetic precursor with the primary MGCT. Genomic, transcriptomic and epigenetic features of testicular GCTs have been extensively studied, allowing for the understanding of GCT development and transformation of seminomatous and nonseminomatous histologies. However, MGCTs are still lacking proper multi-omics analysis and only few data are reported in the literature. Understanding of the mechanism involved in the development, in the progression and in their higher resistance to common therapies is still poorly understood. With this review, we aim to collect all molecular findings reported in this rare disease, resuming the similarities and disparities with the gonadal counterparts.
Orazio Caffo, Cinzia Ortega, Franco Nolè, Donatello Gasparro, Claudia Mucciarini, Michele Aieta, Vittorina Zagonel, Roberto Iacovelli, Ugo De Giorgi, Gaetano Facchini,et al.
Elsevier BV
Nicole Brighi, Vincenza Conteduca, Cristian Lolli, Giorgia Gurioli, Giuseppe Schepisi, Michela Palleschi, Marita Mariotti, Chiara Casadei, and Ugo De Giorgi
Elsevier BV
Vincenza Conteduca, Emanuela Scarpi, Alberto Farolfi, Nicole Brighi, Lorena Rossi, Giorgia Gurioli, Cristian Lolli, Giuseppe Schepisi, Sara Bleve, Caterina Gianni,et al.
Frontiers Media SA
IntroductionMelphalan, as a bifunctional alkylating agent has been shown to be selectively efficient in BRCA-deficient case reports of epithelial ovarian cancer (EOC). The clinical benefit of melphalan on unselected platinum-resistant EOC population and stratified by BRCA status has not been clearly elucidated. We aimed to determine the response to melphalan in patients with recurrent EOC after platinum-based therapy.Material and MethodsThis retrospective observational study included patients with recurrent EOC treated with melphalan between February 2007 to July 2020. Eligibility criteria included having a histological confirmation of EOC, previous treatment with carboplatin plus paclitaxel regimens, and disease recurrence during treatment with or within 6 months of the end of the platinum-based chemotherapy.ResultsA total of 75 platinum-resistant EOC patients were enrolled. Median age was 69 years (range 41-82). Median of previous therapies before melphalan was 4 (range 1-7). We observed a median follow-up of 32 months (range 1-62), progression-free survival (PFS) and overall survival (OS) of 3.6 months (range 2.9-4.7) and 9.5 months (range 8.0-14.1), respectively. In the whole population, 1 complete response, 6 partial responses and 37 stable diseases were registered with an overall clinical benefit rate of 58.7%. In BRCA1/2 mutant patients, we showed a significant longer PFS compared to BRCA1/2 wild type patients (6.2 versus 2.6 months; hazard ratio (HR) 0.25, 95% confidence interval (CI) 0.10-0.61; p=0.002). Moreover, a trend was seen for BRCA1/2 mutants to have a better OS (25.9 versus 8.0 months; HR 0.38; 95% CI 0.12-1.19; p=0.097).ConclusionsOur study represents the largest cohort of heavily-pretreated EOC patients receiving melphalan treatment. Here, we report a considerable clinical activity of melphalan chemotherapy, more evident in a subset of BRCA1/2 mutated patients. Prospective studies to validate these findings are warranted.
Vincenza Conteduca, Daniel Wetterskog, Elena Castro, Emanuela Scarpi, Nuria Romero-Laorden, Giorgia Gurioli, Anuradha Jayaram, Cristian Lolli, Giuseppe Schepisi, Anna Wingate,et al.
Elsevier BV
M. Del Re, V. Conteduca, S. Crucitta, G. Gurioli, C. Casadei, G. Restante, G. Schepisi, C. Lolli, F. Cucchiara, R. Danesi,et al.
Springer Science and Business Media LLC
Abstract Background Androgen receptor (AR) signaling inhibitors represent the standard treatment in metastatic castration resistance prostate cancer (mCRPC) patients. However, some patients display a primary resistance, and several studies investigated the role of the AR as a predictive biomarker of response to treatment. This study is aimed to evaluate the role of AR in liquid biopsy to predict clinical outcome to AR signaling inhibitors in mCRPC patients. Methods Six milliliters of plasma samples were collected before first-line treatment with abiraterone or enzalutamide. Circulating free DNA (cfDNA) and exosome-RNA were isolated for analysis of AR gain and AR splice variant 7 (AR-V7), respectively, by digital droplet PCR. Results Eighty-four mCRPC patients received abiraterone (n = 40) or enzalutamide (n = 44) as first-line therapy. Twelve patients (14.3%) presented AR gain and 30 (35.7%) AR-V7+ at baseline. Median progression-free survival (PFS) and overall survival (OS) were significantly longer in AR-V7− vs AR-V7+ patients (24.3 vs 5.4 months, p < 0.0001; not reached vs 16.2 months, p = 0.0001, respectively). Patients carrying the AR gain had a median PFS of 4.8 vs 24.3 months for AR normal patients (p < 0.0001). Median OS was significantly longer in AR normal vs patients with AR gain (not reached vs 8.17 months, p < 0.0001). A significant correlation between AR-V7 and AR gain was observed (r = 0.28; p = 0.01). The AR gain/AR-V7 combined analysis confirmed a strong predictive effect for biomarkers combination vs patients without any AR aberration (PFS 3.8 vs 28 month, respectively; OS 6.1 vs not reached, respectively; p < 0.0001). Conclusions The present study demonstrates that cfDNA and exosome-RNA are both a reliable source of AR variants and their combined detection in liquid biopsy predicts resistance to AR signaling inhibitors.
Giuseppe Schepisi, Caterina Gianni, Sara Bleve, Silvia De Padova, Cecilia Menna, Cristian Lolli, Alessia Filograna, Vincenza Conteduca, Milena Urbini, Valentina Gallà,et al.
MDPI AG
Testicular cancer (TC) is the most frequent tumor in young males. In the vast majority of cases, it is a curable disease; therefore, very often patients experience a long survival, also due to their young age at diagnosis. In the last decades, the role of the vitamin D deficiency related to orchiectomy has become an increasingly debated topic. Indeed, vitamin D is essential in bone metabolism and many other metabolic pathways, so its deficiency could lead to various metabolic disorders especially in long-term TC survivors. In our article, we report data from studies that evaluated the incidence of hypovitaminosis D in TC survivors compared with cohorts of healthy peers and we discuss molecular mechanisms and clinical implications.
Giuseppe Schepisi, Chiara Casadei, Ilaria Toma, Giulia Poti, Maria Laura Iaia, Alberto Farolfi, Vincenza Conteduca, Cristian Lolli, Giorgia Ravaglia, Nicole Brighi,et al.
MDPI AG
Gynecological tumors are malignancies with both high morbidity and mortality. To date, only a few chemotherapeutic agents have shown efficacy against these cancer types (only ovarian cancer responds to several agents, especially platinum-based combinations). Within this context, the discovery of immune checkpoint inhibitors has led to numerous clinical studies being carried out that have also demonstrated their activity in these cancer types. More recently, following the development of chimeric antigen receptor (CAR)-T cell therapy in hematological malignancies, this strategy was also tested in solid tumors, including gynecological cancers. In this article, we focus on the molecular basis of gynecological tumors that makes them potential candidates for immunotherapy. We also provide an overview of the main immunotherapy studies divided by tumor type and report on CAR technology and the studies currently underway in the area of gynecological malignancies.
Silvia De Padova, Milena Urbini, Giuseppe Schepisi, Alessandra Virga, Elena Meggiolaro, Lorena Rossi, Francesco Fabbri, Tatiana Bertelli, Paola Ulivi, Federica Ruffilli,et al.
Frontiers Media SA
Testicular cancer (TC) is the most frequent solid tumor diagnosed in young adult males. Although it is a curable tumor, it is frequently associated with considerable short-term and long-term morbidity. Both biological and psychological stress experienced during cancer therapy may be responsible for stimulating molecular processes that induce premature aging and deterioration of immune system (immunosenescence) in TC survivors, leading to an increased susceptibility to infections, cancer, and autoimmune diseases. Immunosenescence is a remodeling of immune cell populations with inversion of the CD4:CD8 ratio, accumulation of highly differentiated memory cells, shrinkage of telomeres, shift of T-cell response to Th2 type, and release of pro-inflammatory signals. TC survivors exposed to chemotherapy show features of immunological aging, including an increase in memory T-cells (CD4+ and CD8+) and high expression of the senescence biomarker p16INK4a in CD3+ lymphocytes. However, the plethora of factors involved in the premature aging of TC survivors make the situation more complex if we also take into account the psychological stress and hormonal changes experienced by patients, as well as the high-dose chemotherapy and hematopoietic stem cell transplantation that some individuals may be required to undergo. The relatively young age and the long life expectancy of TC patients bear witness to the importance of improving quality of life and of alleviating long-term side-effects of cancer treatments. Within this context, the present review takes an in-depth look at the molecular mechanisms of immunosenescence, describing experimental evidence of cancer survivor aging and highlighting the interconnected relationship between the many factors modulating the aging of the immune system of TC survivors.
Vincenza Conteduca, Nicole Brighi, Donato Conteduca, Sara Bleve, Caterina Gianni, Giuseppe Schepisi, Maria Laura Iaia, Giorgia Gurioli, Cristian Lolli, and Ugo De Giorgi
Informa UK Limited
ABSTRACT Introduction: Prostate cancer is one of the most frequent tumors worldwide. Due to the lack of reliable markers, patients are usually diagnosed at a late stage when it becomes castration-resistant prostate cancer (CRPC) with a worse outcome. Thus, it is essential to ameliorate the clinical management of these patients. Nowadays, the use of liquid biopsy represents a minimally invasive way to provide a complete molecular landscape of prostate cancer. Thus, this review aims to outline the clinical value of cell-free DNA in real-time monitoring of metastatic CRPC (mCRPC). Areas covered: This comprehensive review explores in detail the characteristics as well as clinical applications of plasma DNA analysis in mCRPC. Expert opinion: The assessment of circulating tumor DNA fraction is a valid and robust biomarker in mCRPC able to predict clinical outcome and monitor disease evolution during treatment. Recently, several methods (i.e. next generation sequencing and digital droplet PCR) are used to investigate genomics in cell-free DNA and novel nanotechnology-based approaches are currently under evaluation in order to improve clinical management of mCRPC patients.
Vincenza Conteduca, Giulia Poti, Paola Caroli, Sabino Russi, Nicole Brighi, Cristian Lolli, Giuseppe Schepisi, Antonino Romeo, Federica Matteucci, Giovanni Paganelli,et al.
SAGE Publications
Over the years, an increasing proportion of metastatic prostate cancer patients has been found to experience an initial bone flare phenomenon under both standard therapies (androgen deprivation therapy, chemotherapy, radiotherapy, abiraterone, enzalutamide) and novel agents (immunotherapy, bone-targeting radioisotopes). The underlying biological mechanisms of the flare phenomenon are still elusive and need further clarification, particularly in relation to different types of treatment and their treatment response assessment. Flare phenomenon is often underestimated and, in some cases, can negatively affect clinical outcome. In cases with suspected bone flare, the treatment should be continued for a minimum of 12 more weeks before further decisions about efficacy can be taken. Physicians and patients should be aware of this effect to avoid unwarranted anxiety and inadequate early discontinuation of treatment. This review aims at highlighting new evidence on flare phenomenon arising after the introduction of new drugs extending across the biochemical, radiographic and clinical spectrum of the disease.