|
1
|
Schepisi G, Urbini M, Casadei C, Gallà V, Rossetti S, Basso U, Lolli C, Gurioli G, Petracci E, Cecere SC, Ventriglia J, Zampiga V, Miserocchi A, Cangini I, De Santis I, Di Napoli M, Menna C, Mambelli G, Pignata S, De Giorgi U. Olaparib as a rescue treatment in platinum-refractory germ-cell tumors: the IGG-02 phase II trial. ESMO Open 2025; 10:105056. [PMID: 40279883 DOI: 10.1016/j.esmoop.2025.105056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 03/18/2025] [Accepted: 03/19/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND Therapeutic options for patients with advanced germ-cell tumors (GCTs) after multiple relapses or resistant disease are limited. Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair. PATIENTS AND METHODS In this proof-of principle open-label, single-arm, phase II trial of olaparib 300 mg twice daily in patients with relapsed/refractory metastatic germ-cell cancer [IGG-02 study (NCT02533765)], patient eligibility included failure after high-dose chemotherapy or after at least two different cisplatin-based regimens. RESULTS Between September 2015 and February 2019, 18 patients, with a median age of 39 years (range 22-61 years) were enrolled. Severe adverse events (AEs) were observed in seven patients. There were no partial responses, five cases (27.8%) with stable disease (SD) lasting 3, 4, 4, 7 and 43 months, and 13 (72.2%) progressive disease. A germline DNA repair profile panel showed only a BRCA1-mutated case associated with an SD lasting for 4 months. The long-lasting patient on olaparib (43 months) experienced a myelodisplastic syndrome (MDS) associated with the onset of a pathogenic mutation affecting PPM1D. CONCLUSIONS Olaparib as a single agent demonstrated no activity in heavily pretreated GCT patients. Future studies with PARP inhibitors should be planned in less-pretreated GCT patients based on molecular analysis to support better patient selection.
Collapse
Affiliation(s)
- G Schepisi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy.
| | - M Urbini
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - C Casadei
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - V Gallà
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - S Rossetti
- Department of Urogynaecological Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione G Pascale' IRCCS, Naples, Italy
| | - U Basso
- Medical Oncology Unit 1, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy
| | - C Lolli
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - G Gurioli
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - E Petracci
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - S C Cecere
- Department of Urogynaecological Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione G Pascale' IRCCS, Naples, Italy
| | - J Ventriglia
- Department of Urogynaecological Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione G Pascale' IRCCS, Naples, Italy
| | - V Zampiga
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - A Miserocchi
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - I Cangini
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - I De Santis
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - M Di Napoli
- Department of Urogynaecological Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione G Pascale' IRCCS, Naples, Italy
| | - C Menna
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - G Mambelli
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - S Pignata
- Department of Urogynaecological Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione G Pascale' IRCCS, Naples, Italy
| | - U De Giorgi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| |
Collapse
|
|
2
|
Scalia G, Ferini G, Shams Z, Graziano F, Ponzo G, Giurato E, Galasso MG, Pumo V, Caruso M, Galvano G, Marrone S, Naimo J, Nicoletti GF, Umana GE. Spinal Metastases in Non-Seminomatous Germ Cell Testicular Tumors: Prognosis and Integrated Therapeutic Approaches-A Systematic Review with an Institutional Case Illustration. Curr Oncol 2024; 31:7459-7475. [PMID: 39727674 DOI: 10.3390/curroncol31120551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Revised: 11/11/2024] [Accepted: 11/22/2024] [Indexed: 12/28/2024] Open
Abstract
(1) Background: Testicular cancer, although accounting for only 0.5% to 1% of all solid male cancers, is the most common malignancy in males aged 15 to 35 years. Non-seminomatous germ cell tumors (NSGCT) represent nearly half of all testicular germ cell tumors and are associated with a more aggressive clinical course. Spinal metastases, while rare, pose significant challenges due to their potential to cause spinal cord compression, neurological deficits, and severe pain. This systematic review aims to evaluate prognosis and treatment approaches for spinal metastases in NSGCT, with a focus on multidisciplinary care and treatment outcomes. (2) Methods: A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, and Embase were searched on 18 September 2024, using the Boolean search strategy [(Nonseminomatous germ cell tumor (NSGCT) AND (spinal OR vertebral metastases)]. Case reports, case series, and cohort studies providing detailed patient data were included. Data on patient demographics, tumor histology, metastatic site, treatments, and outcomes were extracted for analysis. (3) Results: A total of 164 cases of NSGCT with spinal metastases were analyzed, with patients aged 23 to 40 years (median: 31.5 years). The lumbar spine was involved in all cases, and spinal cord compression occurred in 59.8% of patients, often causing severe neurological symptoms such as cauda equina syndrome. Chemotherapy, primarily cisplatin-based, was administered in all cases, while surgical interventions, including laminectomy and vertebrectomy, were performed in cases of spinal compression and instability. Complete remission occurred in only 2.4% of patients. Progressive improvement was observed in 56.7% of cases, while 20.1% of patients died. Outcomes varied, highlighting the importance of individualized, multidisciplinary care to manage both systemic and localized disease. (4) Conclusions: Spinal metastases in NSGCT represent a complex clinical scenario, requiring a combination of chemotherapy, surgery, and in some cases, radiotherapy. Chemotherapy remains essential, but surgery is critical for addressing spinal compression and instability. A multidisciplinary approach is vital for optimizing outcomes, as prognosis is variable, with some patients achieving improvement while others face progressive disease or death. Further research is needed to refine the role of radiotherapy and improve long-term treatment strategies for this rare complication.
Collapse
Affiliation(s)
- Gianluca Scalia
- Neurosurgery Unit, Department of Head and Neck Surgery, Garibaldi Hospital, 95124 Catania, Italy
- Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy
| | - Gianluca Ferini
- Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy
- Department of Radiation Oncology, REM Radioterapia srl, 95029 Viagrande, Italy
| | - Zubayer Shams
- Brunel Medical School, Brunel University London, Uxbridge, London UB8 3PH, UK
| | - Francesca Graziano
- Neurosurgery Unit, Department of Head and Neck Surgery, Garibaldi Hospital, 95124 Catania, Italy
| | - Giancarlo Ponzo
- Neurosurgery Unit, Department of Head and Neck Surgery, Garibaldi Hospital, 95124 Catania, Italy
| | - Eliana Giurato
- Anatomic Pathology Unit, Garibaldi Hospital, 95124 Catania, Italy
| | | | | | | | - Gianluca Galvano
- Department of Diagnostic Imaging, Interventional Radiology and Neuroradiology, Garibaldi Hospital, 95124 Catania, Italy
| | - Salvatore Marrone
- Department of Neurosurgery, Sant' Elia Hospital, 93100 Caltanissetta, Italy
| | - Jessica Naimo
- Pain Therapy and Palliative Care Unit, ASP 7 Ragusa, 97100 Ragusa, Italy
| | | | - Giuseppe Emmanuele Umana
- Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy
- Department of Neurosurgery, Trauma Center, Gamma Knife Center, Cannizzaro Hospital, 95126 Catania, Italy
| |
Collapse
|
|
3
|
Topal A, Erturk I, Koseoglu C, Dumludag A, Kuzu ÖF, Karadurmus B, Kaplan Tuzun E, Atacan H, Mammadzada N, Yildirim G, Acar R, Karadurmus N. Salvage Treatment for Extragonadal Germ Cell Tumours: High-Dose Chemotherapy and Autologous Stem Cell Transplantation Outcomes-A Single-Centre Experience. J Clin Med 2024; 13:6494. [PMID: 39518633 PMCID: PMC11547118 DOI: 10.3390/jcm13216494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 10/27/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
Objective: Extragonadal germ cell tumours have a more unfavourable prognosis than gonadal germ cell tumours. We aimed to evaluate the survival analysis, response rates, and factors affecting responses to high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) in patients with relapsed/refractory extragonadal germ cell tumours. Methods: This study included patients diagnosed with extragonadal germ cell tumours who underwent HDCT + ASCT between November 2016 and January 2023 at Gülhane Training and Research Hospital. Clinical characteristics and follow-up data from patient records and the hospital's electronic system were retrospectively analysed. Patients under 18 years of age and those without medical records were excluded. Patient characteristics, post-HDCT progression-free survival (PFS), overall survival (OS) data, and factors affecting survival were examined. The relationship between clinical factors and OS/PFS was analysed. Results: Twenty-five patients were included in this study. Complete response (CR) was observed in seven patients (28%), partial response (PR) was observed in nine patients (36%), stable disease (SD) was observed in one patient, and progressive disease (PD) was observed in eight patients (32%) after HDCT + ASCT. The median follow-up period was 25.4 months. The median PFS and OS after HDCT + ASCT were calculated as 6.1 months and 12.2 months, respectively. Conclusions: Salvage HDCT + ASCT is an option in the treatment of extragonadal germ cell tumours, offering the potential for prolonged survival and curing.
Collapse
Affiliation(s)
- Alper Topal
- Division of Medical Oncology, Department of Internal Medicine, Gulhane Research & Training Hospital, Ankara 06010, Türkiye; (I.E.); (C.K.); (A.D.); (Ö.F.K.); (B.K.); (E.K.T.); (H.A.); (N.M.); (G.Y.); (R.A.); (N.K.)
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
4
|
Richardson NH, Taza F, Abonour R, Althouse SK, Ashkar R, Abu Zaid M, Hanna NH, Kesler KA, Adra N, Einhorn LH. High-dose chemotherapy and peripheral blood stem cell transplantation as salvage therapy in primary mediastinal nonseminomatous germ cell tumors: The Indiana University experience. Cancer 2024; 130:3115-3122. [PMID: 38768296 DOI: 10.1002/cncr.35375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 04/08/2024] [Accepted: 04/10/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND Patients with relapsed primary mediastinal nonseminomatous germ cell tumor have low cure rates with salvage chemotherapy or surgery. The authors report survival outcomes of patients who received high-dose chemotherapy (HDCT) and peripheral blood stem cell transplantation (PBSCT) at Indiana University. METHODS The prospectively maintained Indiana University germ cell tumor database identified 32 patients with primary mediastinal nonseminomatous germ cell tumor who progressed after first-line cisplatin-based combination chemotherapy and received HDCT and PBSCT between 2006 and 2021. Therapy included two consecutive courses of HDCT consisting of 700 mg/m2 carboplatin and 750 mg/m2 etoposide, each for 3 consecutive days, and each followed by PBSCT. A second course was not given if the patient experienced progressive disease or prohibitive toxicity. Progression-free survival and overall survival were analyzed using the Kaplan-Meier method. Medians with 95% confidence intervals were also calculated along with 2-year probabilities. RESULTS The median age at HDCT was 30 years (range, 18-61 years). With a median follow-up of 4.7 years (range, 1-14 years), the 2-year progression-free survival rate was 31% (95% confidence interval, 16%-47%), and the 2-year overall survival rate was 35% (95% confidence interval, 19%-52%). At last follow-up, nine patients (28%) remained without evidence of disease, including two platinum-refractory patients and two patients who were receiving HDCT as third-line therapy. There were three treatment-related deaths. CONCLUSIONS Salvage HDCT and PBSCT is an active combination in patients who have relapsed primary mediastinal nonseminomatous germ cell tumor with curative potential and prolonged survival, including in platinum-refractory and third-line settings. The authors recommend this approach for initial salvage chemotherapy in this patient population.
Collapse
Affiliation(s)
- Noah H Richardson
- Division of Hematology and Medical Oncology, Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Fadi Taza
- Division of Hematology and Medical Oncology, Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Rafat Abonour
- Division of Hematology and Medical Oncology, Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Sandra K Althouse
- Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Ryan Ashkar
- Division of Hematology and Medical Oncology, Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Mohammad Abu Zaid
- Division of Hematology and Medical Oncology, Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Nassar H Hanna
- Division of Hematology and Medical Oncology, Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Kenneth A Kesler
- Department of Surgery, Community Health Network, Indianapolis, Indiana, USA
| | - Nabil Adra
- Division of Hematology and Medical Oncology, Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Lawrence H Einhorn
- Division of Hematology and Medical Oncology, Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
| |
Collapse
|
|
5
|
Secondino S, Badoglio M, Rosti G, Labopin M, Delaye M, Bokemeyer C, Seidel C, Kanfer E, Metafuni E, Finke J, Bouhris JH, Kosmas C, Malard F, Pagani A, Kuball J, Koehl U, Ruggeri A, De Giorgi U, Pedrazzoli P. High-dose chemotherapy with autologous stem cell transplants in adult primary non-seminoma mediastinal germ-cell tumors. A report from the Cellular Therapy and Immunobiology working party of the EBMT. ESMO Open 2024; 9:103692. [PMID: 39241498 PMCID: PMC11408034 DOI: 10.1016/j.esmoop.2024.103692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/31/2024] [Accepted: 08/01/2024] [Indexed: 09/09/2024] Open
Abstract
BACKGROUND Primary mediastinal germ-cell tumors (PMGCTs) account for 1%-3% of all germ-cell tumors (GCTs). Non-seminoma have a poorer prognosis compared to their gonadal counterpart and, according to the International Germ Cell Cancer Collaborative Group, they are considered 'poor risk' disease. Medical treatment is the same, with overall survival (OS) being ∼40%, declining to 10%-15% at 3 years in case of lung and non-visceral metastases. Patients failing first-line chemotherapy have a dismal prognosis, with only 5%-10% of cases being cured in the salvage setting. High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been successfully used to treat patients with relapsed or refractory gonadal GCTs. PATIENTS AND METHODS This retrospective study aimed to investigate the value of HDC with ASCT in the whole population and define primary mediastinal non seminoma germ cell tumor (PMNSGCT) patient subgroups, who were registered in the European Society for Blood and Marrow Transplantation database from January 2000 to January 2018. Sixty-nine adult male patients with PMNSGCT were included. HDC consisted mainly of carboplatin/etoposide doublet, and most patients received HDC as part of a multiple sequential HDC program. RESULTS OS was 43.3% at 2 years, and 34.7% at 5 and 10 years for the entire cohort. Analysis of outcomes showed that patients undergoing HDC as upfront therapy had a better progression-free survival (PFS) and OS compared to those treated in subsequent relapses (5-year PFS 51.8% versus 26.8% and 5-year OS 51.3% versus 25.9%). Better remission status before transplantation was predictive of the benefit of HDC. Three treatment-related deaths were recorded. CONCLUSIONS To our knowledge, this is the most extensive retrospective study of HDC in PMNSGCTs patients and the first to thoroughly investigate potential predictors of benefit from this treatment. HDC with ASCT may well represent a therapeutic option in patients with PMNSGCTs after the first relapse or even as a front-line program.
Collapse
Affiliation(s)
- S Secondino
- Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
| | | | - G Rosti
- Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - M Delaye
- Department of Medical Oncology and Cellular Therapy, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Tenon University Hospital, Paris, France
| | - C Bokemeyer
- Department of Internal Medicine II, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - C Seidel
- Department of Internal Medicine II, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - E Kanfer
- Imperial College Heathcare NHS Trust, London, UK
| | - E Metafuni
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - J Finke
- Department of Internal Medicine I, Hematology, Oncology and Stem Cell Transplantation, Freiburg University, Freiburg, Germany
| | | | - C Kosmas
- Metaxa Hospital, Piraeus, Greece
| | - F Malard
- Sorbonne Université, Centre de Recherche Saint-Antoine INSERM UMRs938, Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France
| | - A Pagani
- Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - J Kuball
- Department of Hematology and Center for Translational Immunology, UMC Ultrecht, Utrecht, The Netherlands
| | - U Koehl
- Institute of Clinical Immunology and Fraunhofer Institute for Cell Therapy and Immunology, Leipzig
| | | | | | - P Pedrazzoli
- Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy
| |
Collapse
|
|
6
|
Evmorfopoulos K, Marsitopoulos K, Karachalios R, Karathanasis A, Dimitropoulos K, Tzortzis V, Zachos I, Vlachostergios PJ. The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors. Cancers (Basel) 2024; 16:428. [PMID: 38275869 PMCID: PMC10814346 DOI: 10.3390/cancers16020428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 01/16/2024] [Accepted: 01/17/2024] [Indexed: 01/27/2024] Open
Abstract
Testicular germ cell tumors (TGCTs) are cancers with very good prognosis, even in the metastatic setting, with high curative potential mainly attributed to the introduction of cisplatin-based chemotherapy. However, approximately 15% of the patients develop platinum-refractory disease and suffer multiple relapses. Therefore, there is an unmet need for novel therapeutic agents with improved efficacy and minimal long-term side effects. Recent advances in the development of immunotherapeutic agents, particularly immune checkpoint inhibitors (ICIs), have offered an opportunity to test their activity in various tumor types, including GCTs. This review aims to analyze the immune microenvironment of these tumors and present the most recently available data from studies that have tested immunotherapeutic agents against GCTs. The majority of the available knowledge derives from case reports or small cohort studies, particularly those involving ICIs of the PD-1/PD-L1 axis alone or in combination with anti-CTLA-4 monoclonal antibodies. Other immunotherapeutic targeted approaches, including antibody-drug conjugates, antibody prodrugs, vaccines, tyrosine kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapy, have biological rationales and have shown preliminary activity or are currently being tested. Growing evidence on these and other approaches will assist in broadening the currently limited treatment armamentarium against platinum-refractory TGCTs.
Collapse
Affiliation(s)
- Konstantinos Evmorfopoulos
- Department of Urology, School of Health Sciences, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece (V.T.)
| | - Konstantinos Marsitopoulos
- Department of Urology, School of Health Sciences, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece (V.T.)
| | - Raphael Karachalios
- Department of Urology, School of Health Sciences, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece (V.T.)
| | - Athanasios Karathanasis
- Department of Urology, School of Health Sciences, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece (V.T.)
| | | | - Vassilios Tzortzis
- Department of Urology, School of Health Sciences, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece (V.T.)
| | - Ioannis Zachos
- Department of Urology, School of Health Sciences, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece (V.T.)
| | - Panagiotis J. Vlachostergios
- Department of Urology, School of Health Sciences, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece (V.T.)
- Department of Medical Oncology, IASO Thessalias Hospital, 41500 Larissa, Greece
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA
| |
Collapse
|
|
7
|
Urbini M, Bleve S, Schepisi G, Menna C, Gurioli G, Gianni C, De Giorgi U. Biomarkers for Salvage Therapy in Testicular Germ Cell Tumors. Int J Mol Sci 2023; 24:16872. [PMID: 38069192 PMCID: PMC10706346 DOI: 10.3390/ijms242316872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 11/24/2023] [Accepted: 11/25/2023] [Indexed: 12/18/2023] Open
Abstract
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.
Collapse
Affiliation(s)
- Milena Urbini
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy;
| | - Sara Bleve
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy; (S.B.); (G.S.); (C.M.); (C.G.); (U.D.G.)
| | - Giuseppe Schepisi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy; (S.B.); (G.S.); (C.M.); (C.G.); (U.D.G.)
| | - Cecilia Menna
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy; (S.B.); (G.S.); (C.M.); (C.G.); (U.D.G.)
| | - Giorgia Gurioli
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy;
| | - Caterina Gianni
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy; (S.B.); (G.S.); (C.M.); (C.G.); (U.D.G.)
| | - Ugo De Giorgi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy; (S.B.); (G.S.); (C.M.); (C.G.); (U.D.G.)
| |
Collapse
|
|
8
|
Schepisi G, Gianni C, Cursano MC, Gallà V, Menna C, Casadei C, Bleve S, Lolli C, Martinelli G, Rosti G, De Giorgi U. Immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR)-T cell therapy: Potential treatment options against Testicular Germ Cell Tumors. Front Immunol 2023; 14:1118610. [PMID: 36860862 PMCID: PMC9968831 DOI: 10.3389/fimmu.2023.1118610] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 02/03/2023] [Indexed: 02/15/2023] Open
Abstract
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.
Collapse
Affiliation(s)
- Giuseppe Schepisi
- 1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy,*Correspondence: Giuseppe Schepisi,
| | - Caterina Gianni
- 1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Maria Concetta Cursano
- 1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Valentina Gallà
- 2Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Cecilia Menna
- 1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Chiara Casadei
- 1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Sara Bleve
- 1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Cristian Lolli
- 1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Giovanni Martinelli
- 1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Giovanni Rosti
- 1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Ugo De Giorgi
- 1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| |
Collapse
|
|
9
|
Bleve S, Cursano MC, Casadei C, Schepisi G, Menna C, Urbini M, Gianni C, De Padova S, Filograna A, Gallà V, Rosti G, Barone D, Chovanec M, Mego M, De Giorgi U. Inflammatory Biomarkers for Outcome Prediction in Patients With Metastatic Testicular Cancer. Front Oncol 2022; 12:910087. [PMID: 35756636 PMCID: PMC9226315 DOI: 10.3389/fonc.2022.910087] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 04/26/2022] [Indexed: 11/13/2022] Open
Abstract
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.
Collapse
Affiliation(s)
- Sara Bleve
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Maria Concetta Cursano
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Chiara Casadei
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Giuseppe Schepisi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Cecilia Menna
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Milena Urbini
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Caterina Gianni
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Silvia De Padova
- Psycho-Oncology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Alessia Filograna
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Valentina Gallà
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Giovanni Rosti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Domenico Barone
- Radiology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Michal Chovanec
- 2nd Department of Oncology, Comenius University, Faculty of Medicine, National Cancer Institute, Bratislava, Slovakia
| | - Michal Mego
- 2nd Department of Oncology, Comenius University, Faculty of Medicine, National Cancer Institute, Bratislava, Slovakia
| | - Ugo De Giorgi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| |
Collapse
|
|
10
|
Giunta EF, Ottaviano M, Mosca A, Banna GL, Rescigno P. Standard versus high-dose chemotherapy in mediastinal germ cell tumors: a narrative review. MEDIASTINUM (HONG KONG, CHINA) 2022; 6:6. [PMID: 35340836 PMCID: PMC8841545 DOI: 10.21037/med-21-29] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 09/22/2021] [Indexed: 06/14/2023]
Abstract
OBJECTIVE The aim of this review is to analyze feasibility and toxicities of high-dose chemotherapy (HDCT) in comparison to standard dose chemotherapy (SDCT) in patients affected by mediastinal germ cell tumors (MGCTs), discussing factors that may affect therapeutic choices, such as: management of residual disease, early response predictors for chemotherapeutic efficacy and determinants of chemotherapeutic resistance. In this review, we discuss the main clinical experiences with HDCT and SDCT in germ cell tumor (GCT) patients specifically in those affected by MGCT. BACKGROUND MGCTs represent a very small subset characterized by a poor prognosis, despite improvements in their clinical management and in understanding their biology. From early 1970s, HDCT has become an alternative to SDCT for both first-line and salvage therapeutic settings in advanced GCT patients. Several HDCT schedules-either cisplatin or carboplatin-based-have been tested so far, both in clinical randomized trial and in single-center experiences, with divergent results in terms of clinical outcomes and tolerability. Moreover, the majority of these studies included, but were not exclusively designed for, advanced MGCT patients, making difficult to infer data for this specific subset. METHODS an extended review of literature through PubMed was conducted using the keywords "mediastinal germinal cell tumors", "standard dose chemotherapy" and "high dose chemotherapy". CONCLUSIONS HDCT regimens could not be considered to date a standard option as first-line therapy in advanced MGCT patients, whilst they could be an alternative to SDCT regimens in relapsed tumors after proper patient selection.
Collapse
Affiliation(s)
- Emilio Francesco Giunta
- Department of Precision Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
| | - Margaret Ottaviano
- Oncology Unit, Ospedale del Mare, Naples, Italy
- CRCTR Coordinating Rare Tumors Reference Center of Campania Region, Naples, Italy
| | - Alessandra Mosca
- Multidisciplinary Outpatient Oncology Clinic, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy
| | - Giuseppe Luigi Banna
- Department of Oncology, Portsmouth Hospitals University NHS Trust, Portsmouth PO2 8QD, UK
| | - Pasquale Rescigno
- Interdisciplinary Group for Translational Research and Clinical Trials, Urological Cancers (GIRT-Uro), Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy
| |
Collapse
|
|
11
|
Marandino L, Vogl UM. Mediastinal germ cell tumours: where we are and where we are going-a narrative review. MEDIASTINUM (HONG KONG, CHINA) 2022; 6:7. [PMID: 35340835 PMCID: PMC8841536 DOI: 10.21037/med-21-33] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 11/26/2021] [Indexed: 05/21/2023]
Abstract
OBJECTIVE In this review, we summarize the current state of the art of primary mediastinal germ cell tumours (PMGCTs) and we highlight challenges and future research directions for this disease. BACKGROUND PMGCTs account for 1-3% of all germ cell malignancies and for 15% of adult anterior mediastinal cancers. In 60-70% of cases PMGCTs are represented by nonseminomatous germ cell tumours (GCTs), and in 30-40% of cases by seminomas. Even if PMGCTs share histological and biochemical characteristics with gonadal GCTs, they have peculiar clinical and biological features. Nonseminomatous PMGCTs have a poor prognosis, with a 5-year overall survival (OS) rate of 40-50% after platinum-based chemotherapy and surgery, and a long-term OS of only 10% after salvage treatment. Due to the rarity of this disease, no level 1 evidence is available from randomised trials for PMGCTs. The combination of bleomycin, etoposide, and cisplatin (BEP) or etoposide, ifosfamide and cisplatin (VIP) for 4 cycles are recommended as first line treatment options for nonseminomatous PMGCTs. Surgery of the residual disease after chemotherapy is fundamental in the treatment of nonseminomatous PMGCTs. PMGCTs have high TP53 pathway gene alterations, while targetable gene alterations are rarely identified, thus challenging the advance of precision medicine in this field. METHODS We performed a narrative review of international literature published in English on PMGCTs, focusing the attention on clinical trials, international guidelines and translational studies. CONCLUSIONS Treatment of patients with PMGCTs is challenging and should be performed in experienced centers. International collaborations should become a priority to ensure optimal patient management. Clinical investigation of new therapeutic options remains an important unmet clinical need, and inclusion of patients in clinical trials should be encouraged. Liquid biopsy is a new promising strategy in PMGCTs.
Collapse
Affiliation(s)
- Laura Marandino
- Service of medical oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland
| | - Ursula Maria Vogl
- Service of medical oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland
| |
Collapse
|
|
12
|
Primary Mediastinal and Testicular Germ Cell Tumors in Adolescents and Adults: A Comparison of Genomic Alterations and Clinical Implications. Cancers (Basel) 2021; 13:cancers13205223. [PMID: 34680371 PMCID: PMC8533956 DOI: 10.3390/cancers13205223] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 10/11/2021] [Accepted: 10/14/2021] [Indexed: 11/28/2022] Open
Abstract
Simple Summary The germ cell tumors (GCTs) family is a heterogeneous group of neoplasms that includes tumors affecting testis (TGCTs) and rarer cases occurring in extragonadal sites. Mediastinal germ cell tumors (MGCTs) are more aggressive and have poorer prognosis. Due to their rarity of MGCTs, few molecular and clinical studies are reported. MGCTs share biological similarities with TGCT, and international guidelines recommend use of the same therapies validated for TGCT. However, while high response rate is achieved in TGCT, MGCT tend to be resistant to therapy. This review resumes all molecular findings reported in MGCTs, summarizing molecular characteristics common with TGCT and highlighting the different molecular alterations that characterize mediastinal tumors. A deeper understanding of the MGCT biology will help in clinical management of these patients. Abstract 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.
Collapse
|
|
13
|
El-Zaatari ZM, Ro JY. Mediastinal Germ Cell Tumors: A Review and Update on Pathologic, Clinical, and Molecular Features. Adv Anat Pathol 2021; 28:335-350. [PMID: 34029275 DOI: 10.1097/pap.0000000000000304] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Mediastinal germ cell tumors (MGCTs) are the most common extragonadal germ cell tumors (GCTs) and most often arise in the anterior mediastinum with a male predilection. MGCTs also have a predilection for patients with Klinefelter syndrome and possibly other genetic conditions. MGCTs, as GCTs at other extragonadal sites, are thought to arise from germ cells improperly retained during migration along the midline during embryogenesis. Similar to their counterparts in the testes, MGCTs are classified into seminomatous and nonseminomatous GCTs. Seminomatous MGCT represents pure seminoma, whereas nonseminomatous MGCTs encompass pure yolk sac tumors, embryonal carcinoma, choriocarcinoma, mature or immature teratoma, and mixed GCTs with any combination of GCT types, including seminoma. Somatic-type or hematologic malignancies can also occur in association with a primary MGCT. MGCTs share molecular findings with GCTs at other sites, most commonly the presence of chromosome 12p gains and isochromosome i(12p). Treatment includes neoadjuvant chemotherapy followed by surgical resection of residual tumor, with the exception of benign teratomas, which require only surgical resection without chemotherapy. In this review, we highlight and provide an update on pathologic, clinical, and molecular features of MGCTs. Immunohistochemical profiles of each tumor type, as well as differential diagnostic considerations, are discussed.
Collapse
Affiliation(s)
- Ziad M El-Zaatari
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX
| | - Jae Y Ro
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX
- Weill Medical College of Cornell University (WCMC), New York, NY
| |
Collapse
|
|
14
|
Schepisi G, Gianni C, Bleve S, De Padova S, Menna C, Lolli C, Filograna A, Conteduca V, Urbini M, Gallà V, Casadei C, Rosti G, De Giorgi U. Vitamin D Deficiency in Testicular Cancer Survivors: A Systematic Review. Int J Mol Sci 2021; 22:5145. [PMID: 34067977 PMCID: PMC8152282 DOI: 10.3390/ijms22105145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 05/08/2021] [Accepted: 05/10/2021] [Indexed: 11/16/2022] Open
Abstract
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.
Collapse
Affiliation(s)
- Giuseppe Schepisi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy; (C.G.); (S.B.); (C.M.); (C.L.); (A.F.); (V.C.); (C.C.); (G.R.); (U.D.G.)
| | - Caterina Gianni
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy; (C.G.); (S.B.); (C.M.); (C.L.); (A.F.); (V.C.); (C.C.); (G.R.); (U.D.G.)
| | - Sara Bleve
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy; (C.G.); (S.B.); (C.M.); (C.L.); (A.F.); (V.C.); (C.C.); (G.R.); (U.D.G.)
| | - Silvia De Padova
- Psycho-Oncology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy;
| | - Cecilia Menna
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy; (C.G.); (S.B.); (C.M.); (C.L.); (A.F.); (V.C.); (C.C.); (G.R.); (U.D.G.)
| | - Cristian Lolli
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy; (C.G.); (S.B.); (C.M.); (C.L.); (A.F.); (V.C.); (C.C.); (G.R.); (U.D.G.)
| | - Alessia Filograna
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy; (C.G.); (S.B.); (C.M.); (C.L.); (A.F.); (V.C.); (C.C.); (G.R.); (U.D.G.)
| | - Vincenza Conteduca
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy; (C.G.); (S.B.); (C.M.); (C.L.); (A.F.); (V.C.); (C.C.); (G.R.); (U.D.G.)
| | - Milena Urbini
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy;
| | - Valentina Gallà
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy;
| | - Chiara Casadei
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy; (C.G.); (S.B.); (C.M.); (C.L.); (A.F.); (V.C.); (C.C.); (G.R.); (U.D.G.)
| | - Giovanni Rosti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy; (C.G.); (S.B.); (C.M.); (C.L.); (A.F.); (V.C.); (C.C.); (G.R.); (U.D.G.)
| | - Ugo De Giorgi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola, Italy; (C.G.); (S.B.); (C.M.); (C.L.); (A.F.); (V.C.); (C.C.); (G.R.); (U.D.G.)
| |
Collapse
|
|
15
|
Joel A, Mathew N, Andugala SS, Daniel S, Gnanamuthu BR, John AO, Georgy JT, Chacko RT, Irodi A, Yadav B, John S, Singh A. Primary mediastinal germ cell tumours: real world experience in the low middle income (LMIC) setting. Ecancermedicalscience 2021; 15:1186. [PMID: 33777179 PMCID: PMC7987494 DOI: 10.3332/ecancer.2021.1186] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Indexed: 11/11/2022] Open
Abstract
PURPOSE Primary mediastinal germ cell tumours (PMGCTs) are rare; with limited data available about their outcomes and optimal treatment in the low middle income countries setting. We studied the clinical profile of patients with PMGCT treated at our centre in order to estimate their survival outcomes and to identify prognostic factors affecting the same. PATIENTS AND METHODS Fifty-seven patients with PMGCTs treated between April 2001 and June 2019 were included. Baseline characteristics, details of first line chemotherapy, response rates, toxicity and surgical outcomes were noted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS Among 57 male patients (seminoma = 20 and nonseminomatous = 37), the median follow-up was 10 months (range: 1-120 months). For mediastinal seminoma, 9 (45%) and 11 (55%) patients had good and intermediate risk disease, respectively. Nineteen patients (95%) received BEP (Bleomycin, etoposide and cisplatin) chemotherapy. 94.7% had partial responses and median event-free survival was not reached. All patients were alive and disease free at 2 years. For primary mediastinal nonseminomatous germ cell tumours (PMNSGCTs), all patients were poor risk. Thirty-four (91.8%) received BEP/EP chemotherapy as first line. Responses were PRM+ (partial response with elevated markers) in 7 (20.5%) and PRM- in 12 (35.2%). The incidence of febrile neutropenia was 50% and 55.8% in seminole and PMNSGCT, respectively. The median OS was 9.06 months and median PFS was 4.63 months for PMNSGCT. The proportion of patients alive at 1 year and 2 years were 35% and 24.3%, respectively. CONCLUSION Primary mediastinal seminomas are rarer and have better survival outcomes. Treatment of PMNSGCT is still a challenge and is associated with poorer survival outcomes.
Collapse
Affiliation(s)
- Anjana Joel
- Department of Medical Oncology, Christian Medical College and Hospital Vellore, Vellore 632004, India
| | - Namrata Mathew
- Department of Medical Oncology, Christian Medical College and Hospital Vellore, Vellore 632004, India
| | - Shalom Sylvester Andugala
- Department of Thoracic Surgery, Christian Medical College and Hospital Vellore, Vellore 632004, India
| | - Sherin Daniel
- Department of Pathology, Christian Medical College and Hospital Vellore, Vellore 632004, India
| | - Birla Roy Gnanamuthu
- Department of Thoracic Surgery, Christian Medical College and Hospital Vellore, Vellore 632004, India
| | - Ajoy Oommen John
- Department of Medical Oncology, Christian Medical College and Hospital Vellore, Vellore 632004, India
| | - Josh Thomas Georgy
- Department of Medical Oncology, Christian Medical College and Hospital Vellore, Vellore 632004, India
| | - Raju Titus Chacko
- Department of Medical Oncology, Christian Medical College and Hospital Vellore, Vellore 632004, India
| | - Aparna Irodi
- Department of Radiology, Christian Medical College and Hospital Vellore, Vellore 632004, India
| | - Bijesh Yadav
- Department of Biostatistics, Christian Medical College and Hospital Vellore, Vellore 632004, India
| | - Subhashini John
- Department of Radiotherapy, Christian Medical College and Hospital Vellore, Vellore 632004, India
| | - Ashish Singh
- Department of Medical Oncology, Christian Medical College and Hospital Vellore, Vellore 632004, India
| |
Collapse
|
|
16
|
De Padova S, Urbini M, Schepisi G, Virga A, Meggiolaro E, Rossi L, Fabbri F, Bertelli T, Ulivi P, Ruffilli F, Casadei C, Gurioli G, Rosti G, Grassi L, De Giorgi U. Immunosenescence in Testicular Cancer Survivors: Potential Implications of Cancer Therapies and Psychological Distress. Front Oncol 2021; 10:564346. [PMID: 33520693 PMCID: PMC7844142 DOI: 10.3389/fonc.2020.564346] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 11/23/2020] [Indexed: 01/13/2023] Open
Abstract
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.
Collapse
Affiliation(s)
- Silvia De Padova
- Psycho-Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Milena Urbini
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Giuseppe Schepisi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Alessandra Virga
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Elena Meggiolaro
- Psycho-Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Lorena Rossi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Francesco Fabbri
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Tatiana Bertelli
- Psycho-Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Paola Ulivi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Federica Ruffilli
- Psycho-Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Chiara Casadei
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Giorgia Gurioli
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Giovanni Rosti
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Luigi Grassi
- Institute of Psychiatry, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara and University Hospital Psychiatry Unit, Integrated Department of Mental Health S. Anna University Hospital and Health Authorities, Ferrara, Italy
| | - Ugo De Giorgi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| |
Collapse
|
|
17
|
Şahin U, Demirer T. Graft-versus-cancereffect and innovative approaches in thetreatment of refractory solid tumors. Turk J Med Sci 2020; 50:1697-1706. [PMID: 32178508 PMCID: PMC7672351 DOI: 10.3906/sag-1911-112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 03/14/2020] [Indexed: 12/23/2022] Open
Abstract
Background/aim Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been used for the treatment of various refractory solid tumors during the last two decades. After the demonstration of graft-versus-leukemia (GvL) effect in a leukemic murine model following allo-HSCT from other strains of mice, graft-versus-tumor (GvT) effect in a solid tumor after allo-HSCT has also been reported in a murine model in 1984. Several trials have reported the presence of a GvT effect in patients with various refractory solid tumors, including renal, ovarian and colon cancers, as well as soft tissue sarcomas [1]. The growing data on haploidentical transplants also indicate GvT effect in some pediatric refractory solid tumors. Novel immunotherapy-based treatment modalities aim at inducing an allo-reactivity against the metastatic solid tumor via a GvT effect. Recipient derived immune effector cells (RDICs) in the antitumor reactivity following allo-HSCT have also been considered as an emerging therapy for advanced refractory solid tumors. Conclusion This review summarizes the background, rationale, and clinical results of immune-based strategies using GvT effect for the treatment of various metastatic and refractory solid tumors, as well as innovative approaches such as haploidentical HSCT, CAR-T cell therapies and tumor infiltrating lymphocytes (TIL).
Collapse
Affiliation(s)
- Uğur Şahin
- Hematology Unit, Yenimahalle Education and Research Hospital, Yıldırım Beyazıt University, Ankara, Turkey
| | - Taner Demirer
- Department of Hematology, School of Medicine, Ankara University, Ankara, Turkey
| |
Collapse
|
|
18
|
Cursano MC, Kopf B, Scarpi E, Menna C, Casadei C, Schepisi G, Lolli C, Altavilla A, Gallà V, Santini D, Tonini G, Chovanec M, Mego M, De Giorgi U. Prognostic Role of Systemic Inflammatory Indexes in Germ Cell Tumors Treated With High-Dose Chemotherapy. Front Oncol 2020; 10:1325. [PMID: 32923384 PMCID: PMC7457022 DOI: 10.3389/fonc.2020.01325] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Accepted: 06/25/2020] [Indexed: 12/22/2022] Open
Abstract
High-dose chemotherapy (HDCT) has curative potential in relapsed/refractory germ cell tumors (GCT). Due to the complexity of this population and the toxicity of HDCT, we evaluated the association between blood-based systemic inflammatory indexes and the outcome of GCT patients undergoing salvage treatment with HDCT in order to define additional prognostic factors able to orient clinical decision. Baseline characteristics, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) of 62 patients undergoing HDCT for GCT were retrospectively collected. The aim is to evaluate the correlation between each inflammatory marker (NLR, PLR, and SII) and response to HDCT, overall survival (OS), and progression-free survival (PFS). Using the receiver operating curve to identify the best cutoff values, it was found that patients with GCT with NLR ≥3.3 and SII ≥844,000 had shorter PFS and inferior OS. In the multivariable analysis including inflammatory markers, the International Prognostic Factor Study Group (IPFSG) risk group, age, and previous line of treatment, NLR ≥3.3 and SII ≥844,000 were identified to be independently associated with shorter PFS and OS. Moreover, NLR, PLR, and SII significantly correlate with overall response to HDCT. Associating IPFSG prognostic score to inflammatory markers at baseline of HDCT may improve prognostic information and could help physicians to make more personalized treatment decisions.
Collapse
Affiliation(s)
| | - Barbara Kopf
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Emanuela Scarpi
- Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Cecilia Menna
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Chiara Casadei
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Giuseppe Schepisi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Cristian Lolli
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Amelia Altavilla
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Valentina Gallà
- Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Daniele Santini
- Department of Medical Oncology, University of Rome, Rome, Italy
| | - Giuseppe Tonini
- Department of Medical Oncology, University of Rome, Rome, Italy
| | - Michal Chovanec
- Second Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.,Department of Oncology, National Cancer Institute, Bratislava, Slovakia.,Translational Research Unit, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Michal Mego
- Second Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.,Department of Oncology, National Cancer Institute, Bratislava, Slovakia.,Translational Research Unit, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Ugo De Giorgi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| |
Collapse
|
|
19
|
De Giorgi U, Casadei C, Bergamini A, Attademo L, Cormio G, Lorusso D, Pignata S, Mangili G. Therapeutic Challenges for Cisplatin-Resistant Ovarian Germ Cell Tumors. Cancers (Basel) 2019; 11:cancers11101584. [PMID: 31627378 PMCID: PMC6826947 DOI: 10.3390/cancers11101584] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 10/10/2019] [Accepted: 10/15/2019] [Indexed: 12/13/2022] Open
Abstract
The majority of patients with advanced ovarian germ cell cancer are treated by cisplatin-based chemotherapy. Despite adequate first-line treatment, nearly one third of patients relapse and almost half develop cisplatin-resistant disease, which is often fatal. The treatment of cisplatin-resistant disease is challenging and prognosis remains poor. There are limited data on the efficacy of specific chemotherapeutic regimens, high-dose chemotherapy with autologous progenitor cell support and targeted therapies. The inclusion of patients in clinical trials is strongly recommended, especially in clinical trials on the most frequent male germ cell tumors, to offer wider therapeutic opportunities. Here, we provide an overview of current and potential new treatment options including combination chemotherapy, high-dose chemotherapy and molecular targeted therapies, for patients with cisplatin-resistant ovarian germ cell tumors.
Collapse
Affiliation(s)
- Ugo De Giorgi
- Department of Medical Oncology and Hematology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.
| | - Chiara Casadei
- Department of Medical Oncology and Hematology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.
| | - Alice Bergamini
- Department of Obstetrics and Gynaecology, San Raffaele Scientific Institute, 20132 Milan, Italy.
| | - Laura Attademo
- Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80138 Naples, Italy.
| | - Gennaro Cormio
- Gynecologic Oncology Unit, IRCCS Istituto Oncologico Giovanni Paolo II, 70124 Bari, Italy.
| | - Domenica Lorusso
- Gynecologic Oncology Unit, Department of Woman, Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy.
| | - Sandro Pignata
- Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80138 Naples, Italy.
| | - Giorgia Mangili
- Department of Obstetrics and Gynaecology, San Raffaele Scientific Institute, 20132 Milan, Italy.
| |
Collapse
|
|
20
|
Atilla E, Ataca Atilla P, Cengiz Seval G, Bektaş M, Demirer T. Current approach to early gastrointestinal and liver complications of hematopoietic stem cell transplantation. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:122-131. [PMID: 30459131 DOI: 10.5152/tjg.2018.18156] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The gastrointestinal (GI) system is one of the most commonly affected sites during a hematopoietic stem cell transplantation (HSCT) due to toxicities of preparative regimens, the accompanying immunodeficiency, and organ damage caused by graft versus host disease. In this review, we focus on early GI and liver complications following autologous (auto-) and allogeneic (allo-) HSCT and clarify both the risk factors and therapeutic strategies. Early GI and liver complications associated with HSCT remain challenging issues. Despite the improvements in this field during the last decade, treatments for these complications still place a significant burden on both patients and the physicians treating these patients. GI and liver complications remain some of the causes of mortality associated with HSCT. For practicing hematologists, oncologists, and gastroenterologists in this field, the awareness and early diagnosis of the GI complications remain important factors to obtain optimal outcomes in this patient population.
Collapse
Affiliation(s)
- Erden Atilla
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| | - Pınar Ataca Atilla
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| | - Güldane Cengiz Seval
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| | - Mehmet Bektaş
- Department of Gastroenterology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| | - Taner Demirer
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| |
Collapse
|
|
21
|
Taylor M, Khan S, Stapleton M, Wang J, Chen J, Wynn R, Yabe H, Chinen Y, Boelens JJ, Mason RW, Kubaski F, Horovitz DDG, Barth AL, Serafini M, Bernardo ME, Kobayashi H, Orii KE, Suzuki Y, Orii T, Tomatsu S. Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future. Biol Blood Marrow Transplant 2019; 25:e226-e246. [PMID: 30772512 PMCID: PMC6615945 DOI: 10.1016/j.bbmt.2019.02.012] [Citation(s) in RCA: 128] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 02/11/2019] [Indexed: 12/16/2022]
Abstract
Allogenic hematopoietic stem cell transplantation (HSCT) has proven to be a viable treatment option for a selected group of patients with mucopolysaccharidoses (MPS), including those with MPS types I, II, IVA, VI, and VII. Early diagnosis and timely referral to an expert in MPS are critical, followed by a complete examination and evaluation by a multidisciplinary team, including a transplantation physician. Treatment recommendations for MPS are based on multiple biological, sociological, and financial factors, including type of MPS, clinical severity, prognosis, present clinical signs and symptoms (disease stage), age at onset, rate of progression, family factors and expectations, financial burden, feasibility, availability, risks and benefits of available therapies such as HSCT, enzyme replacement therapy (ERT), surgical interventions, and other supportive care. International collaboration and data review are critical to evaluating the therapeutic efficacy and adverse effects of HSCT for MPS. Collaborative efforts to assess HSCT for MPS have been ongoing since the first attempt at HSCT in a patient with MPS reported in 1981. The accumulation of data since then has made it possible to identify early outcomes (ie, transplantation outcomes) and long-term disease-specific outcomes resulting from HSCT. The recent identification of predictive factors and the development of innovative regimens have significantly improved the outcomes of both engraftment failure and transplantation-related mortality. Assessment of long-term outcomes has considered a variety of factors, including type of MPS, type of graft, age at transplantation, and stage of disease progression, among others. Studies on long-term outcomes are considered a key factor in the use of HSCT in patients with MPS. These studies have shown the effects and limitations of HSCT on improving disease manifestations and quality of life. In this review, we summarize the efficacy, side effects, risks, and cost of HSCT for each type of MPS.
Collapse
Affiliation(s)
- Madeleine Taylor
- Department of Biomedical, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware; Deparment of Biological Science, University of Delaware, Newark, Delaware
| | - Shaukat Khan
- Department of Biomedical, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware
| | - Molly Stapleton
- Department of Biomedical, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware; Deparment of Biological Science, University of Delaware, Newark, Delaware
| | - Jianmin Wang
- Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing Chen
- Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Robert Wynn
- Department of Paediatric Haematology and Cell Therapy, University of Manchester, Manchester, United Kingdom
| | - Hiromasa Yabe
- Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Yasutsugu Chinen
- Department of Pediatrics, Faculty of Medicine, University of the Ryukyus, Nishihara, Japan
| | - Jaap Jan Boelens
- Stem Cell Transplantation and Cellular Therapies, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Robert W Mason
- Department of Biomedical, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware; Deparment of Biological Science, University of Delaware, Newark, Delaware
| | - Francyne Kubaski
- Medical Genetics Service, Hospital de ClÃnicas de Porto Alegre (HCPA), Department of Genetics and Molecular Biology- Program Partnership Graduate in Genetics and Molecular Biology (PPGBM), Federal University of Rio Grande do Sul (UFRGS), and National Institute of Populational Medical Genetics (INAGEMP), Porto Alegre, Brazil
| | - Dafne D G Horovitz
- Medical Genetics Department, National Institute of Women, Children, and Adolescent Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Anneliese L Barth
- Medical Genetics Department, National Institute of Women, Children, and Adolescent Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Marta Serafini
- Department of Pediatrics, Dulbecco Telethon Institute, University of Milano-Bicocca, Monza, Italy
| | - Maria Ester Bernardo
- Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele-Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Hironori Kobayashi
- Department of Pediatrics, Shimane University Faculty of Medicine, Shimane, Japan
| | - Kenji E Orii
- Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Yasuyuki Suzuki
- Medical Education Development Center, Gifu University, Gifu, Japan
| | - Tadao Orii
- Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Shunji Tomatsu
- Department of Biomedical, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware; Department of Pediatrics, Shimane University Faculty of Medicine, Shimane, Japan; Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan; Department of Pediatrics, Thomas Jefferson University, Philadelphia, Pennsylvania.
| |
Collapse
|
|
22
|
Banna GL, Nicolai N, Palmieri G, Ottaviano M, Balzarini L, Barone D, Basso U, Bavila A, Bertoni F, Calliada F, Cai T, Carrafiello G, Condello C, Da Pozzo L, Di Nardo D, Fornarini G, Prayer Galetti T, Garolla A, Giannatempo P, Guerra L, La Spina S, Malatino L, Marchiano' A, Monti M, Morbiato FF, Morelli F, Nole' F, Palazzi S, Procopio G, Rosti G, Sacco C, Salvetti A, Salvioni R, Sava T, Secondino S, Serpentini S, Spreafico C, Tavolini IM, Valcamonico F, Verri E, Zucali P, De Giorgi U. Recommendations for surveillance and follow-up of men with testicular germ cell tumors: a multidisciplinary consensus conference by the Italian Germ cell cancer Group and the Associazione Italiana di Oncologia Medica. Crit Rev Oncol Hematol 2019; 137:154-164. [PMID: 31014511 DOI: 10.1016/j.critrevonc.2019.03.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 03/09/2019] [Accepted: 03/12/2019] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND No compelling evidence is available about surveillance and follow-up of patients with testicular germ cell tumour (TGCT). METHODS In the light of the best clinical evidence, the Italian Germ cell cancer Group (IGG) and the Associazione Italiana di Oncologia Medica (AIOM) set up a multidisciplinary national consensus conference, involving 42 leading experts and 3 TGCT survivors. A minimum of 50% of votes was required in order to achieve a consensus recommendation on 29 questions. RESULTS Recommendations have been summarized in three tables, divided by stage I seminoma, stage I nonseminoma and the advanced disease, which may be useful for clinicians to appropriately choose the clinical investigation and its timing during the surveillance and follow-up of TGCT patients based on an accurate estimation of their risk of disease relapse. CONCLUSIONS The IGG-AIOM consensus recommendations may help clinicians to choose appropriate clinical investigations for the surveillance and follow-up of TGCT patients.
Collapse
Affiliation(s)
- Giuseppe Luigi Banna
- IGG Italian Germ cell cancer Group, Italy; AIOM - Associazione Italiana di Oncologia Medica, Italy.
| | - Nicola Nicolai
- IGG Italian Germ cell cancer Group, Italy; SIU - Società Italiana di Urologia, Italy; AURO - Associazione Italiana Urologi Italiani, Italy
| | | | | | - Luca Balzarini
- IGG Italian Germ cell cancer Group, Italy; SIRM - Società Italiana di Radiologia Medica, Italy
| | - Domenico Barone
- IGG Italian Germ cell cancer Group, Italy; SIRM - Società Italiana di Radiologia Medica, Italy
| | | | | | - Filippo Bertoni
- AIRO - Associazione Italiana di Radioterapia Oncologica, Italy
| | - Fabrizio Calliada
- IGG Italian Germ cell cancer Group, Italy; SIRM - Società Italiana di Radiologia Medica, Italy
| | | | | | | | - Luigi Da Pozzo
- SIU - Società Italiana di Urologia, Italy; SIUrO - Società Italiana di Urologia Oncologica, Italy
| | - Domenico Di Nardo
- AITT - Associazione Italiana Tumore Testicolo, Italy; FAVO - Federazione Italiana delle Associazioni di Volontariato in Oncologia, Italy
| | | | | | | | | | - Luca Guerra
- AIMN - Associazione Italiana Medicina Nucleare e Imaging Molecolare, Italy
| | | | | | - Alfonso Marchiano'
- IGG Italian Germ cell cancer Group, Italy; SIRM - Società Italiana di Radiologia Medica, Italy
| | - Mirko Monti
- AITT - Associazione Italiana Tumore Testicolo, Italy
| | | | | | | | | | | | | | | | - Andrea Salvetti
- SIMG - Società Italiana della Medicina Generale e delle Cure Primarie, Italy
| | | | | | | | | | - Carlo Spreafico
- IGG Italian Germ cell cancer Group, Italy; SIRM - Società Italiana di Radiologia Medica, Italy
| | | | | | | | | | - Ugo De Giorgi
- IGG Italian Germ cell cancer Group, Italy; AIOM - Associazione Italiana di Oncologia Medica, Italy
| |
Collapse
|
|
23
|
Rosti G, Secondino S, Necchi A, Fornarini G, Pedrazzoli P. Primary mediastinal germ cell tumors. Semin Oncol 2019; 46:107-111. [DOI: 10.1053/j.seminoncol.2019.04.001] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 04/05/2019] [Accepted: 04/11/2019] [Indexed: 11/11/2022]
|
|
24
|
Casadei C, Schepisi G, Menna C, Chovanec M, Gurioli G, Gallà V, Altavilla A, Marcellini M, Bellia SR, Lolli C, Mego M, Rosti G, De Giorgi U. Reclassification of good-risk seminoma: prognostic factors, novel biomarkers and implications for clinical management. Future Oncol 2019; 15:1347-1352. [DOI: 10.2217/fon-2018-0850] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Germ cell tumors represent 11% of the cancers diagnosed in adolescent males and are the most common solid tumors in adult men between the ages of 20 and 35. Pure seminoma accounts for around 50% of all testicular germ cell tumors. The prognostic classification of the International Germ Cell Cancer Collaborative Group for good-prognosis seminoma includes both nodal disease and pulmonary visceral metastases. In this article, we analyzed recent data on prognosis and outcome of good-prognosis seminoma to revise the traditional classification of the disease and improve tailored treatment.
Collapse
Affiliation(s)
- Chiara Casadei
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Giuseppe Schepisi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Cecilia Menna
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Michal Chovanec
- Second Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Giorgia Gurioli
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Valentina Gallà
- Unit of Biostatistics & Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Amelia Altavilla
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | | | - Salvatore Roberto Bellia
- Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Cristian Lolli
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Michal Mego
- Second Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Giovanni Rosti
- Department of Oncology, Policlinico San Matteo IRCCS, Pavia, Italy
| | - Ugo De Giorgi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| |
Collapse
|
|
25
|
De Padova S, Casadei C, Berardi A, Bertelli T, Filograna A, Cursano MC, Menna C, Burgio SL, Altavilla A, Schepisi G, Prati S, Montalti S, Chovanec M, Banna GL, Grassi L, Mego M, De Giorgi U. Caregiver Emotional Burden in Testicular Cancer Patients: From Patient to Caregiver Support. Front Endocrinol (Lausanne) 2019; 10:318. [PMID: 31191451 PMCID: PMC6546807 DOI: 10.3389/fendo.2019.00318] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 05/01/2019] [Indexed: 12/15/2022] Open
Abstract
Testicular cancer is the most common tumor in young males aged 15-40 years. The overall cure rate for men with testicular cancer is >90%, so a huge number of these patients will become testicular cancer survivors. These people may feel some stress in the experience of diagnosis, treatment, and consequences that affects the quality of life, and during follow-up, especially when new issues and emotional distresses appear over time, such as late side-effects of treatments and emotional challenges including fear of tumor relapse, fertility and sexuality concerns, and social and workplace issues. The cancer experience has an impact not only on patients, but also on their relatives (e.g., spouses, parents, or siblings), who often have to assume a caregiving role for the duration of and following treatment for cancer. Moreover, the caregiver plays an important role in supporting a man with a testicular cancer, providing physical and emotional care. This review presents a summary of existing knowledge regarding the impact and the burden of testicular cancer on caregivers.
Collapse
Affiliation(s)
- Silvia De Padova
- Psycho-Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | - Chiara Casadei
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | - Alejandra Berardi
- Psycho-Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | - Tatiana Bertelli
- Psycho-Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | - Alessia Filograna
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | | | - Cecilia Menna
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | - Salvatore Luca Burgio
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | - Amelia Altavilla
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | - Giuseppe Schepisi
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | - Sabrina Prati
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | - Sandra Montalti
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | - Michal Chovanec
- Medical Oncology Department, Campus Bio-Medico University, Rome, Italy
- 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia
| | | | - Luigi Grassi
- University Hospital Psychiatry Unit, Integrated Department of Mental Health and Addictive Behavior, St. Anna University Hospital and NHS Community Health Trusts, Ferrara, Italy
| | - Michal Mego
- Medical Oncology Department, Campus Bio-Medico University, Rome, Italy
- 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia
| | - Ugo De Giorgi
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
- *Correspondence: Ugo De Giorgi
| |
Collapse
|
|
26
|
Schepisi G, De Padova S, De Lisi D, Casadei C, Meggiolaro E, Ruffilli F, Rosti G, Lolli C, Ravaglia G, Conteduca V, Farolfi A, Grassi L, De Giorgi U. Psychosocial Issues in Long-Term Survivors of Testicular Cancer. Front Endocrinol (Lausanne) 2019; 10:113. [PMID: 30858829 PMCID: PMC6397854 DOI: 10.3389/fendo.2019.00113] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 02/07/2019] [Indexed: 01/20/2023] Open
Abstract
Testicular cancer is the most frequent tumor in young males aged 15-39 years. As cure rates are currently around 90%, the prevalence of survivors is increasing. However, a disease-free condition does not necessarily correspond to a life free of physical and psychosocial health problems. The aim of this review was to explore psychosocial morbidity among testicular cancer survivors. A literature search was conducted in three electronic databases (PubMed, Medline, and Embase). The results of the search on cancer survivors were then combined with those of the search on psychosocial concerns and work performance. Eighty-four publications met the inclusion criteria. Physical, psychological, work-related problems and changing perspectives about work and life in general influenced life and career decisions among testicular cancer survivors. Individual health, sexual relationships and work problems, affect several important aspects of survival and significantly influence the QoL of long-term survivors.
Collapse
Affiliation(s)
- Giuseppe Schepisi
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
- *Correspondence: Giuseppe Schepisi
| | - Silvia De Padova
- Psycho-Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| | - Delia De Lisi
- Medical Oncology Department, Santa Chiara Hospital, Trento, Italy
| | - Chiara Casadei
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| | - Elena Meggiolaro
- Psycho-Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| | - Federica Ruffilli
- Psycho-Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| | - Giovanni Rosti
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| | - Cristian Lolli
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| | - Giorgia Ravaglia
- Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| | - Vincenza Conteduca
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| | - Alberto Farolfi
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| | - Luigi Grassi
- Hospital Psychiatry Unit, Department of Biomedical and Specialty Surgical Sciences, Integrated Department of Mental Health and Addictive Behavior, Institute of Psychiatry, St. Anna University Hospital and NHS Community Health Trusts, University of Ferrara, Ferrara, Italy
| | - Ugo De Giorgi
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| |
Collapse
|
|
27
|
Cengiz Seval G, Topçuoğlu P, Demirer T. Current Approach to Non-Infectious Pulmonary Complications of Hematopoietic Stem Cell Transplantation. Balkan Med J 2018; 35:131-140. [PMID: 29553463 PMCID: PMC5863250 DOI: 10.4274/balkanmedj.2017.1635] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Hematopoietic stem cell transplantation is an established treatment for patients with a wide range of malignant and nonmalignant conditions. Noninfectious pulmonary complications still remain a leading cause of morbidity and mortality in these patients. Treating hematopoietic stem cell transplantation recipients with noninfectious pulmonary complications is still challenging, and the current treatment armamentarium and strategies are not adequate for patients receiving hematopoietic stem cell transplantation. Further trials are needed for a better description of the pathogenesis and the complete diagnostic criteria as well as for the development of effective therapeutic approaches for the management of noninfectious pulmonary complications of the hematopoietic stem cell transplantation. This review outlines the incidence, risk factors, pathogenesis, and clinical spectrum and discusses the current approaches to the management of noninfectious pulmonary complications of Hematopoietic stem cell transplantation.
Collapse
Affiliation(s)
- Güldane Cengiz Seval
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| | - Pervin Topçuoğlu
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| | - Taner Demirer
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| |
Collapse
|
|
28
|
De Giorgi U, Richard S, Badoglio M, Kanfer E, Bourrhis JH, Nicolas-Virelizier E, Vettenranta K, Lioure B, Martin S, Dreger P, Schuler MK, Thomson K, Scarpi E, Rosti G, Selle F, Mangili G, Lanza F, Bregni M. Salvage high-dose chemotherapy in female patients with relapsed/refractory germ-cell tumors: a retrospective analysis of the European Group for Blood and Marrow Transplantation (EBMT). Ann Oncol 2018; 28:1910-1916. [PMID: 28510616 DOI: 10.1093/annonc/mdx259] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background High-dose chemotherapy (HDC) with hematopoietic progenitor cell transplantation is a standard option for relapsed/refractory testicular germ-cell tumor (GCT), but only few data have been reported in female patients with GCT. We conducted a retrospective analysis of female patients with GCT treated with HDC and registered with the European Society for Blood and Marrow Transplantation. Patients and methods Between 1985 and 2013, 60 registered female patients with GCT, median age 27 years (range 15-48), were treated with salvage HDC. Forty patients (67%) had primary ovarian GCT, 8 (13%) mediastinal, 7 (12%) retroperitoneal and 5 (8%) other primary sites/unknown. Twenty-two patients (37%) received HDC as second-line therapy, 29 (48%) as third-line, and 9 (15%) as fourth- to sixth-line. Nine of 60 patients (15%) received HDC as late-intensification with no evidence of metastasis before HDC. The conditioning HDC regimens comprised carboplatin in 51 of 60 cases (85%), and consisted of a single HDC cycle in 31 cases (52%), a multi-cycle HDC regimen in 29 (48%). Results Nine cases who underwent late intensification HDC were not evaluable for response. Of the other 51 assessable patients, 17 (33%) achieved a complete response (CR), 8 (16%) a marker-negative partial remission (PRm-), 5 (10%) a marker-positive partial remission, 5 (10%) stable disease, and 13 (25%) progressive disease. There were 3 toxic deaths (6%). With an overall median follow-up of 14 months (range 1-219), 7 of 9 (78%) patients with late intensification and 18 of the 25 patients (72%) achieving a CR/PRm- following HDC were free of relapse/progression. In total, 25 of 60 patients (42%) were progression-free following HDC at a median follow-up of 87 months (range 3-219 months). Conclusions Salvage HDC based on carboplatin represents a therapeutic option for female patients with relapsed/refractory GCT.
Collapse
Affiliation(s)
- U De Giorgi
- Department of Medical Oncology and Hematology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - S Richard
- Department of Medical Oncology, Hopital Tenon, Paris
| | | | - E Kanfer
- Department of Hematology, Imperial College, Hammersmith Hospital, London, UK
| | - J H Bourrhis
- Hematology-Marrow Transplant Service, Institute Gustave-Roussy, Villejuif
| | | | - K Vettenranta
- Department of Pediatrics, University of Helsinki, Helsinki, Finland
| | - B Lioure
- Department of Hematology/Oncology, Strasbourg University Hospital, Strasbourg, France
| | - S Martin
- Department of Internal Medicine II, Robert-Bosch-Hospital, Stuttgart
| | - P Dreger
- Department of Medicine V, University of Heidelberg, Heidelberg
| | - M K Schuler
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany
| | - K Thomson
- Department of Haematology, University College London Hospital, London, UK
| | - E Scarpi
- Biostatistics and Clinical Trials Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola
| | - G Rosti
- Department of Oncology, Policlinico San Matteo IRCCS, Pavia
| | - F Selle
- Department of Medical Oncology, Hopital Tenon, Paris
| | - G Mangili
- Department of Obstetrics and Gynaecology, San Raffaele Scientific Institute, Milan
| | - F Lanza
- Department of Onco-Hematology, Santa Maria delle Croci Hospital, Ravenna
| | - M Bregni
- Department of Medical Oncology, Busto Arsizio Hospital, Busto Arsizio, Italy
| | | |
Collapse
|
|
29
|
Schepisi G, De Padova S, Scarpi E, Lolli C, Gurioli G, Menna C, Burgio SL, Rossi L, Gallà V, Casadio V, Salvi S, Conteduca V, De Giorgi U. Vitamin D status among long-term survivors of testicular cancer. Oncotarget 2018; 8:36780-36786. [PMID: 28030821 PMCID: PMC5482697 DOI: 10.18632/oncotarget.14167] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 11/08/2016] [Indexed: 12/02/2022] Open
Abstract
A correlation between disturbances in hormone levels and the onset of metabolic disorders has been reported in long-term survivors of testicular cancer (TC). We evaluated serum vitamin D levels and other biological parameters in a consecutive series of 61 long-term (≥3 years) unilateral TC survivors with a median a follow-up of 4 years and in a cohort of healthy males. Deficient vitamin D levels were observed in 10 (17%) of the 58 long-term unilateral TC survivors but were not reported in healthy males (p=.019, Fisher test). Median vitamin D levels were 18.6 ug/L in 58 assessable TC survivors and 23.6 ug/L in 40 healthy males (p=.031). In univariate logistic regression analysis, TC diagnosis was associated with inadequate levels of vitamin D (p=.047). Vitamin D levels were lower when follow-up was > 10 years, albeit this difference was not statistically significant (p=.074). Long-term (especially > 10 years) TC survivors may have difficulty maintaining optimal vitamin D levels. Larger studies are needed to better characterize vitamin D status and possible correlations with premature hormonal aging reported in long-term TC survivors.
Collapse
Affiliation(s)
- Giuseppe Schepisi
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| | - Silvia De Padova
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| | - Emanuela Scarpi
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| | - Cristian Lolli
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| | - Giorgia Gurioli
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| | - Cecilia Menna
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| | - Salvatore L Burgio
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| | - Lorena Rossi
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| | - Valentina Gallà
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| | - Valentina Casadio
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| | - Samanta Salvi
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| | - Vincenza Conteduca
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| | - Ugo De Giorgi
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 40 I-47014 Meldola, FC, Italy
| |
Collapse
|
|
30
|
Romano FJ, Rossetti S, Conteduca V, Schepisi G, Cavaliere C, Di Franco R, La Mantia E, Castaldo L, Nocerino F, Ametrano G, Cappuccio F, Malzone G, Montanari M, Vanacore D, Quagliariello V, Piscitelli R, Pepe MF, Berretta M, D'Aniello C, Perdonà S, Muto P, Botti G, Ciliberto G, Veneziani BM, De Falco F, Maiolino P, Caraglia M, Montella M, De Giorgi U, Facchini G. Role of DNA repair machinery and p53 in the testicular germ cell cancer: a review. Oncotarget 2018; 7:85641-85649. [PMID: 27821802 PMCID: PMC5356765 DOI: 10.18632/oncotarget.13063] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 10/19/2016] [Indexed: 12/21/2022] Open
Abstract
Notwithstanding the peculiar sensitivity to cisplatin-based treatment, resulting in a very high percentage of cures even in advanced stages of the disease, still we do not know the biological mechanisms that make Testicular Germ Cell Tumor (TGCT) “unique” in the oncology scene. p53 and MDM2 seem to play a pivotal role, according to several in vitro observations, but no correlation has been found between their mutational or expression status in tissue samples and patients clinical outcome. Furthermore, other players seem to be on stage: DNA Damage Repair Machinery (DDR) , especially Homologous Recombination (HR) proteins, above all Ataxia Telangiectasia Mutated (ATM), cooperates with p53 in response to DNA damage, activating apoptotic cascade and contributing to cell “fate”. Homologous Recombination deficiency has been assumed to be a Germ Cell Tumor characteristic underlying platinum-sensitivity, whereby Poly(ADP-ribose) polymerase (PARP), an enzyme involved in HR DNA repair, is an intriguing target: PARP inhibitors have already entered in clinical practice of other malignancies and trials are recruiting TGCT patients in order to validate their role in this disease. This paper aims to summarize evidence, trying to outline an overview of DDR implications not only in TGCT curability, but also in resistance to chemotherapy.
Collapse
Affiliation(s)
- Francesco Jacopo Romano
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy
| | - Sabrina Rossetti
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori 'Fondazione G. Pascale', IRCCS, Naples, Italy
| | - Vincenza Conteduca
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| | - Giuseppe Schepisi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| | - Carla Cavaliere
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto, Taranto, Italy
| | - Rossella Di Franco
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', IRCCS, Napoli, Italy
| | - Elvira La Mantia
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Pathology Unit, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy
| | - Luigi Castaldo
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Department of Uro-Gynaecological Oncology, Division of Urology, Istituto Nazionale Tumori 'Fondazione G. Pascale', IRCCS, Naples, Italy
| | - Flavia Nocerino
- Epidemiology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', IRCCS, Napoli, Italy
| | - Gianluca Ametrano
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', IRCCS, Napoli, Italy
| | - Francesca Cappuccio
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Psicology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', IRCCS, Napoli, Italy
| | - Gabriella Malzone
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Pathology Unit, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy
| | - Micaela Montanari
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", Naples, Italy
| | - Daniela Vanacore
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy
| | - Vincenzo Quagliariello
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy
| | - Raffaele Piscitelli
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Pharmacy Unit, Istituto Nazionale Tumori, Istituto Nazionale Tumori-Fondazione G. Pascale Naples, Italy
| | - Maria Filomena Pepe
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Pathology Unit, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy
| | - Massimiliano Berretta
- Department of Medical Oncology, CRO Aviano, National Cancer Institute, Aviano, Italy
| | - Carmine D'Aniello
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Division of Medical Oncology, A.O.R.N. dei COLLI "Ospedali Monaldi-Cotugno-CTO", Napoli, Italy
| | - Sisto Perdonà
- Department of Uro-Gynaecological Oncology, Division of Urology, Istituto Nazionale Tumori 'Fondazione G. Pascale', IRCCS, Naples, Italy
| | - Paolo Muto
- Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', IRCCS, Napoli, Italy
| | - Gerardo Botti
- Pathology Unit, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy
| | - Gennaro Ciliberto
- Scientific Directorate, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', IRCCS, Napoli, Italy
| | - Bianca Maria Veneziani
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", Naples, Italy
| | - Francesco De Falco
- Psicology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', IRCCS, Napoli, Italy
| | - Piera Maiolino
- Pharmacy Unit, Istituto Nazionale Tumori, Istituto Nazionale Tumori-Fondazione G. Pascale Naples, Italy
| | - Michele Caraglia
- Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy
| | - Maurizio Montella
- Epidemiology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', IRCCS, Napoli, Italy
| | - Ugo De Giorgi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
| | - Gaetano Facchini
- Progetto ONCONET2.0, Linea Progettuale 14 per L'implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy.,Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori 'Fondazione G. Pascale', IRCCS, Naples, Italy
| |
Collapse
|
|
31
|
Abstract
Germ cell tumors are rare neoplasms that affect young males. Nearly 99% of patients with localized stage I disease and nearly 80% of patients with metastatic disease can be cured. Even patients who relapse following chemotherapy can achieve a long-term survival in approximately 30–40% of cases. The main objective in early stages and in good prognosis patients has changed in recent years, and it has become of major importance to reduce treatment-related morbidity without compromising the excellent long-term survival rate. In poor prognosis patients, there is a correlation between the experience of the treating institution and the long-term clinical outcome of the patients, particularly when the most sophisticated therapies are needed. So far, of utmost importance is the information from updated practice guidelines for the diagnosis and treatment of germ cell tumors. The Italian Germ cell cancer Group (IGG) has developed the following clinical recommendations, which identify the current standards in diagnosis and treatment of germ cell tumors in adult males.
Collapse
|
|
32
|
Bozdağ SC, Yüksel MK, Demirer T. Adult Stem Cells and Medicine. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1079:17-36. [DOI: 10.1007/5584_2018_184] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
|
|
33
|
Sahin U, Demirer T. Current strategies for the management of autologous peripheral blood stem cell mobilization failures in patients with multiple myeloma. J Clin Apher 2017; 33:357-370. [DOI: 10.1002/jca.21591] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Revised: 09/09/2017] [Accepted: 09/11/2017] [Indexed: 12/22/2022]
Affiliation(s)
- Ugur Sahin
- Department of Hematology; Ankara University Medical School; Ankara Turkey
| | - Taner Demirer
- Department of Hematology; Ankara University Medical School; Ankara Turkey
| |
Collapse
|
|
34
|
Atilla E, Atilla PA, Toprak SK, Demirer T. A review of late complications of allogeneic hematopoietic stem cell transplantations. Clin Transplant 2017; 31. [PMID: 28753218 DOI: 10.1111/ctr.13062] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/24/2017] [Indexed: 12/13/2022]
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and curative treatment of different malignant and non-malignant diseases. Early transplant-related mortality after allo-HSCT has decreased with reduced-intensity conditioning regimens and effective anti-infectious treatments, but late transplant-related mortality is still a problem. Physicians are now paying more attention to late complications that may worsen the quality of life of many transplant recipients. Chronic graft versus host disease (cGVHD) is one of the major causes of late transplant-related mortality after allo-HSCT. This review discusses recent advances that have been made in clinical evaluation and treatment of late transplant-related complications including cGVHD. The different sites of involvement are organs, especially the skin and eye, and the gastrointestinal, endocrinologic, metabolic, renal, cardiologic, pulmonary, connective tissue, and neurological systems. In addition, this review includes infections and secondary malignancies in post-transplant settings that worsen quality of life in long-term follow-ups.
Collapse
Affiliation(s)
- Erden Atilla
- Department of Hematology, Ankara University Medical School, Ankara, Turkey
| | - Pinar Ataca Atilla
- Department of Hematology, Ankara University Medical School, Ankara, Turkey
| | | | - Taner Demirer
- Department of Hematology, Ankara University Medical School, Ankara, Turkey
| |
Collapse
|
|
35
|
Atilla E, Atilla PA, Bozdağ SC, Demirer T. A review of infectious complications after haploidentical hematopoietic stem cell transplantations. Infection 2017; 45:403-411. [PMID: 28417421 DOI: 10.1007/s15010-017-1016-1] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 04/05/2017] [Indexed: 01/13/2023]
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation from haploidentical donor is a feasible option for patients with hematological diseases who lack a suitable HLA-matched donor, but viral and fungal infections are still the most common causes of morbidity and mortality in haploidentical transplantation setting because of delayed immune reconstitution, increased risk of graft vs host disease (GvHD) or systemic steroid use. Therefore, this review will focus on the infectious complications after haploidentical hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS Electronic publications were searched until February 2017 throughout databases, including Pubmed, Cochrane, and Embase. The following keywords were used 'haploidentical transplantation', 'infection', 'T cell replete', and 'T cell deplete'. RESULTS An increased incidence of bacterial, fungal, or viral infections is detected in haplo-HSCT compared to related, unrelated, or cord blood transplantations. Neutropenia and use of systemic steroid for GvHD and delayed immune reconstitution are important risk factors for infection after haplo-HSCT. CONCLUSION A shift towards T cell repletes haplo-HSCT with post-transplant cyclophosphamide (CY) for GvHD has been emerged in recent years, in which the incidence of viral and fungal infections is detected to be lower. Prophylaxis and pre-emptive treatment strategies should be applied according to patient status.
Collapse
Affiliation(s)
- Erden Atilla
- Department of Hematology, Ankara University Medical School, Cebeci, 06590, Ankara, Turkey
| | - Pinar Ataca Atilla
- Department of Hematology, Ankara University Medical School, Cebeci, 06590, Ankara, Turkey
| | - Sinem Civriz Bozdağ
- Department of Hematology, Ankara University Medical School, Cebeci, 06590, Ankara, Turkey
| | - Taner Demirer
- Department of Hematology, Ankara University Medical School, Cebeci, 06590, Ankara, Turkey.
| |
Collapse
|
|
36
|
Atilla E, Toprak SK, Demirer T. Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation. Turk J Haematol 2017; 34:1-9. [PMID: 27956374 PMCID: PMC5451667 DOI: 10.4274/tjh.2016.0450] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2016] [Accepted: 12/08/2016] [Indexed: 01/19/2023] Open
Abstract
Iron overload is an adverse prognostic factor for patients undergoing hematopoietic stem cell transplantation (HSCT). In the HSCT setting, pretransplant and early posttransplant ferritin and transferrin saturation were found to be highly elevated due to high transfusion requirements. In addition to that, post-HSCT iron overload was shown to be related to infections, hepatic sinusoidal obstruction syndrome, mucositis, liver dysfunction, and acute graft-versus-host disease. Hyperferritinemia causes decreased survival rates in both pre- and posttransplant settings. Serum ferritin levels, magnetic resonance imaging, and liver biopsy are diagnostic tools for iron overload. Organ dysfunction due to iron overload may cause high mortality rates and therefore sufficient iron chelation therapy is recommended in this setting. In this review the management of iron overload in adult HSCT is discussed.
Collapse
Affiliation(s)
| | | | - Taner Demirer
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey Phone : +90 532 325 10 65 E-mail:
| |
Collapse
|
|
37
|
Atilla E, Ataca Atilla P, Demirer T. A Review of Myeloablative vs Reduced Intensity/Non-Myeloablative Regimens in Allogeneic Hematopoietic Stem Cell Transplantations. Balkan Med J 2017; 34:1-9. [PMID: 28251017 PMCID: PMC5322516 DOI: 10.4274/balkanmedj.2017.0055] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 01/19/2017] [Indexed: 02/07/2023] Open
Abstract
Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment option for both malignant and some benign hematological diseases. During the last decade, many of the newer high-dose regimens in different intensity have been developed specifically for patients with hematologic malignancies and solid tumors. Today there are three main approaches used prior to allogeneic transplantation: Myeloablative (MA), Reduced Intensity Conditioning (RIC) and Non-MA (NMA) regimens. MA regimens cause irreversible cytopenia and there is a requirement for stem cell support. Patients who receive NMA regimen have minimal cytopenia and this type of regimen can be given without stem cell support. RIC regimens do not fit the criteria of MA and NMA: the cytopenia is reversible and the stem cell support is necessary. NMA/RIC for Allo-HSCT has opened a new era for treating elderly patients and those with comorbidities. The RIC conditioning was used for 40% of all Allo-HSCT and this trend continue to increase. In this paper, we will review these regimens in the setting of especially allogeneic HSCT and our aim is to describe the history, features and impact of these conditioning regimens on specific diseases.
Collapse
Affiliation(s)
- Erden Atilla
- Department of Hematology, Ankara University School of Medicine, Ankara, Turkey
| | - Pınar Ataca Atilla
- Department of Hematology, Ankara University School of Medicine, Ankara, Turkey
| | - Taner Demirer
- Department of Hematology, Ankara University School of Medicine, Ankara, Turkey
| |
Collapse
|
|
38
|
Ataca Atilla P, Bakanay Ozturk SM, Demirer T. How to manage poor mobilizers for high dose chemotherapy and autologous stem cell transplantation? Transfus Apher Sci 2016; 56:190-198. [PMID: 28034547 DOI: 10.1016/j.transci.2016.11.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Revised: 11/16/2016] [Accepted: 11/26/2016] [Indexed: 12/15/2022]
Abstract
Today, peripheral blood stem cells are the preferred source of stem cells over bone marrow. Therefore, mobilization plays a crutial role in successful autologous stem cell transplantation. Poor mobilization is generally defined as failure to achieve the target level of at least 2×106 CD34+ cells/kg body weight. There are several strategies to overcome poor mobilization: 1) Larger volume Leukapheresis (LVL) 2) Re-mobilization 3) Plerixafor 4) CM+Plerixafor (P)+G-CSF and 5) Bone Marrow Harvest. In this review, the definitions of successful and poor mobilization are discussed. Management strategies for poor mobilization are defined. The recent research on new agents are included.
Collapse
Affiliation(s)
- Pinar Ataca Atilla
- Department of Hematology, Ankara University Medical School, Cebeci, 06590 Ankara, Turkey.
| | | | - Taner Demirer
- Department of Hematology, Ankara University Medical School, Cebeci, 06590 Ankara, Turkey.
| |
Collapse
|
|
39
|
Karadurmus N, Sahin U, Basgoz BB, Arpaci F, Demirer T. Review of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in solid tumors excluding breast cancer. World J Transplant 2016; 6:675-681. [PMID: 28058217 PMCID: PMC5175225 DOI: 10.5500/wjt.v6.i4.675] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 11/01/2016] [Accepted: 11/22/2016] [Indexed: 02/05/2023] Open
Abstract
Solid tumors in adults constitute a heterogeneous group of malignancy originating from various organ systems. Solid tumors are not completely curable by chemotherapy, even though some subgroups are very chemo-sensitive. Recently, oncologists have focused on the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced intensity conditioning (RIC) for the treatment of some refractory solid tumors. After the demonstration of allogeneic graft-versus-leukemia effect in patients with hematological malignancies who received allo-HSCT, investigators evaluated this effect in patients with refractory metastatic solid tumors. According to data from experimental animal models and preliminary clinical trials, a graft-versus-tumor (GvT) effect may also be observed in the treatment of some solid tumors (e.g., renal cell cancer, colorectal cancer, etc.) after allo-HSCT with RIC. The use of RIC regimens offers an opportunity of achieving full-donor engraftment with GvT effect, as well as, a reduced transplant-related mortality. Current literature suggests that allo-HSCT with RIC might become a choice for elderly and medically fragile patients with refractory metastatic solid tumors.
Collapse
|
|
40
|
An overview of hematopoietic stem cell transplantation related thrombotic complications. Crit Rev Oncol Hematol 2016; 107:149-155. [DOI: 10.1016/j.critrevonc.2016.09.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 06/19/2016] [Accepted: 09/21/2016] [Indexed: 02/07/2023] Open
|
|
41
|
Ko JJ, Asif T, Li H, Alimohamed N, Nguyen PT, Heng DY. Disease characteristics and survival outcomes of extragonadal primary germ cell tumour in two Canadian tertiary cancer centres. Can Urol Assoc J 2016; 10:E165-E170. [PMID: 27790297 PMCID: PMC5065405 DOI: 10.5489/cuaj.3357] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Extragonadal germ cell tumours (EGCTs) are a heterogeneous group with distinct natural history and responses to treatment modalities. We sought to evaluate characteristics and survival outcomes in men with EGCTs. METHODS We performed a retrospective analysis on a consecutive list of men diagnosed with EGCT in two Albertan cancer centres between 1990 and 2013. Demographic characteristics and outcomes, stratified by primary site, were evaluated. RESULTS Sixty-nine cases were identified. The median age was 29 (range 15-76) and 48 cases (70%) were non-seminomatous. Twenty-four (35%) belonged to International Germ Cell Cancer Collaborative Group (IGCCCG) favourable risk group, 14 (20%) to intermediate, and 31 (45%) to poor. Thirty (43%) had mediastinal primary (MPs); 29 were treated with first-line bleomycin, etopo-side, and cisplatin (BEP). Seventeen (57%) relapses occurred, of which three patients achieved long-term survival. Seventeen (25%) had a central nervous system (CNS) primary, with eight (47%) classic germinoma. Seven (41%) received primary chemotherapy alone; 5 (29%) received primary radiotherapy alone, and 5 (29%) received both. Nineteen (28%) had a retroperitoneal primary (RPs) and received first-line chemotherapy; all but two received BEP and eight (42%) had surgical resection. Three (5%) had other or unknown primary. Five-year overall survival (OS) and disease-free survival for all patients were 56% and 44%, respectively; for MPs, 44% and 34%; for CNS primary, 76% and 53%; for RPs, 58% and 53%. Factors that correlated with decreased OS were elevated alpha fetoprotein (AFP) (p<0.001) or human chorionic gonadotropin (HCG) (p=0.001), lactate dehydrogenase (LDH) levels (p=0.028), bone metastasis (p<0.001), lung metastasis (p<0.001), and IGCCCG poor risk (p=0.001). CONCLUSIONS EGCT is a rare, but important subset of GCT. Patients with EGCTs, despite aggressive treatments, still have poorer outcomes than gonadal primary.
Collapse
Affiliation(s)
- Jenny J. Ko
- Department of Medical Oncology, Abbotsford Cancer Centre, Abbotsford, BC, Canada
| | - Tehmina Asif
- Department of Medical Oncology, Saskatchewan Cancer Agency, Saskatoon, SK, Canada
| | - Haocheng Li
- Departments of Oncology and Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - Nimira Alimohamed
- Department of Medical Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada
| | - Phuong Thao Nguyen
- Department of Medical Oncology, Royal Inland Cancer Centre, Kamloops, BC, Canada
| | - Daniel Y.C. Heng
- Department of Medical Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada
| |
Collapse
|
|
42
|
Rossi L, Martignano F, Gallà V, Maugeri A, Schepisi G. Impact of Non-Pulmonary Visceral Metastases in the Prognosis and Practice of Metastatic Testicular Germ Cell Tumors. Oncol Rev 2016; 10:292. [PMID: 27471579 PMCID: PMC4943091 DOI: 10.4081/oncol.2016.292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Accepted: 04/07/2016] [Indexed: 12/03/2022] Open
Abstract
Non-pulmonary visceral metastases, in bones, brain and liver, represent nearly the 10% of metastatic sites of advanced germ cell tumors and are associated with poor prognosis. This review article summarizes major evidences on the impact of different visceral sites on the prognosis, treatment and clinical outcome of patients with germ cell tumors. The clinic-biological mechanisms by which these metastatic sites are associated with poor clinical outcome remain unclear. The multimodality treatment showed a potential better survival, in particular in patients with relapsed disease. Patients with advanced germ cell tumors with visceral metastases should be referred to centers with high expertise in the clinical management of such disease.
Collapse
Affiliation(s)
- Lorena Rossi
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)-IRCCS , Meldola (FC), Italy
| | - Filippo Martignano
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)-IRCCS , Meldola (FC), Italy
| | - Valentina Gallà
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)-IRCCS , Meldola (FC), Italy
| | - Antonio Maugeri
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)-IRCCS , Meldola (FC), Italy
| | - Giuseppe Schepisi
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)-IRCCS , Meldola (FC), Italy
| |
Collapse
|
|
43
|
Popovic L, Matovina-Brko G, Popovic M, Petrovic D, Cvetanovic A, Vukojevic J, Jovanovic D. High dose chemotherapy with stem cell support in the treatment of testicular cancer. World J Stem Cells 2015; 7:1222-1232. [PMID: 26730267 PMCID: PMC4691691 DOI: 10.4252/wjsc.v7.i11.1222] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2014] [Revised: 02/23/2015] [Accepted: 11/17/2015] [Indexed: 02/06/2023] Open
Abstract
Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease.
Collapse
|
|
44
|
Necchi A, Giannatempo P, Lo Vullo S, Farè E, Raggi D, Marongiu M, Scanagatta P, Duranti L, Giovannetti R, Girelli L, Nicolai N, Piva L, Biasoni D, Torelli T, Catanzaro M, Stagni S, Maffezzini M, Gianni AM, Mariani L, Pastorino U, Salvioni R. A Prognostic Model Including Pre- and Postsurgical Variables to Enhance Risk Stratification of Primary Mediastinal Nonseminomatous Germ Cell Tumors: The 27-Year Experience of a Referral Center. Clin Genitourin Cancer 2015; 13:87-93.e1. [DOI: 10.1016/j.clgc.2014.06.014] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Revised: 06/07/2014] [Accepted: 06/17/2014] [Indexed: 11/26/2022]
|
|
45
|
Selle F, Gligorov J, Richard S, Khalil A, Alexandre I, Avenin D, Provent S, Soares DG, Lotz JP. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer. ACTA ACUST UNITED AC 2014; 48:13-24. [PMID: 25493378 PMCID: PMC4288488 DOI: 10.1590/1414-431x20144214] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Accepted: 09/15/2014] [Indexed: 02/15/2023]
Abstract
Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.
Collapse
Affiliation(s)
- F Selle
- Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris, France
| | - J Gligorov
- Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris, France
| | - S Richard
- Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris, France
| | - A Khalil
- Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris, France
| | - I Alexandre
- Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges, France
| | - D Avenin
- Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris, France
| | - S Provent
- Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris, France
| | - D G Soares
- Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris, France
| | - J P Lotz
- Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris, France
| |
Collapse
|
|
46
|
Necchi A, Lanza F, Rosti G, Martino M, Farè E, Pedrazzoli P. High-dose chemotherapy for germ cell tumors: do we have a model? Expert Opin Biol Ther 2014; 15:33-44. [PMID: 25243977 DOI: 10.1517/14712598.2015.963051] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Since the late nineties, the intensification of chemotherapy doses with hematopoietic stem cell rescue held promise for patients with advanced and poor prognosis germ cell tumors (GCTs). High-dose chemotherapy (HDCT) has, nowadays, a recognized indication in the salvage setting of advanced GCTs and is steadily utilized worldwide. AREAS COVERED We evaluated the available data with the use of HDCT in these patients. In addition, we provided an original perspective on several issues as experts on behalf of the European Society for Blood and Marrow Transplantation and IGG, including peripheral blood stem cells mobilization and the use of HDCT in special subpopulations of GCT, with the aim to help clarify critical issues in the absence of available clear-cut information. EXPERT OPINION Despite HDCT being currently considered a therapeutic option in the salvage setting, critical questions regarding patient selection are still unanswered. Eligibility of patients with a chemoresistant disease, the use of available prognostic factors as well as tumor marker decline in clinical practice are pending issues. Moving forward, these are critical arguments in favor of further clinical research in the field of advanced GCTs.
Collapse
Affiliation(s)
- Andrea Necchi
- Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Medical Oncology, Medical Oncology 2 Unit , Via G. Venezian 1, 20133 Milano , Italy +39 02 2390 2402 ; +39 02 2390 3150 ;
| | | | | | | | | | | | | |
Collapse
|
|
47
|
Burgio SL, Menna C, Papiani G, Casadei Gardini A, De Luigi N, Corsi R, Rosti G. Alpha-fetoprotein surge following high-dose chemotherapy in germ cell tumours. J Chemother 2013; 25:119-22. [PMID: 23684360 DOI: 10.1179/1973947812y.0000000044] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
In patients with non-seminomatous germ cell tumours (NSGCTs) who receive chemotherapy and have residual disease, a persistently elevated serum marker level after induction chemotherapy indicates active and progressive disease. High-dose chemotherapy (HDCT) is the standard treatment for patients with relapsed NSGCT. We present a case of a patient with residual disease from NSGCT who showed an increase in serum alpha-fetoprotein levels after HDCT, mimicking progression. Resection of the mass did not show viable cells in the tumour specimen, thus suggesting that the elevated level of the marker was expression of hepatic reconstitution after drug-induced liver damage. HDCT is increasingly used in cases of relapsed NSGCT, and the possibility of treatment-induced alpha-fetoprotein elevation must be taken into account in patient management.
Collapse
Affiliation(s)
- Salvatore Luca Burgio
- Department of Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Italy.
| | | | | | | | | | | | | |
Collapse
|
|
48
|
Simonelli M, Rosti G, Banna GL, Pedrazzoli P. Intensified chemotherapy with stem-cell rescue in germ-cell tumors. Ann Oncol 2011; 23:815-22. [PMID: 21948814 DOI: 10.1093/annonc/mdr403] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Based on the high chemosensitivity of germ-cell tumors (GCTs), the concept of high-dose chemotherapy (HDCT) has been developed worldwide and investigated through many clinical trials. It has been carried out in different clinical settings, ranging from resistant or absolute refractory disease to chemosensitive relapse. HDCT with stem-cell support has been also explored as a part of first-line strategy for poor-prognosis patients. PATIENTS AND METHODS Our review summarized results from clinical trials evaluating the role of HDCT in patients with advanced GCTs. So far available data were obtained through a Medline search of English-language literature. RESULTS Several phase II trials and retrospective series have shown a possible benefit for GCT patients with recurrent disease as well as in first-line setting. Despite these results, data derived from randomized phase III studies failed to demonstrate any survival advantage for HDCT over conventional chemotherapy. CONCLUSIONS The role of HDCT in GCTs remains controversial. We need new prospective studies based on prognostic factors with multiple transplants of carboplatin and etoposide as the preferred high dose regimen. At present, based mainly on retrospective and phase II studies, HDCT may represent a therapeutic option for patients with primary refractory disease or for those with a second or further relapse.
Collapse
Affiliation(s)
- M Simonelli
- Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano.
| | | | | | | | | | | |
Collapse
|
|
49
|
Heerema-McKenney A, Bowen J, Hill DA, Suster S, Qualman SJ. Protocol for the Examination of Specimens From Pediatric and Adult Patients With Extragonadal Germ Cell Tumors. Arch Pathol Lab Med 2011; 135:630-9. [DOI: 10.5858/2010-0405-cp.1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
|
|
50
|
Goodwin A, Gurney H, Gottlieb D. Allogeneic bone marrow transplant for refractory mediastinal germ cell tumour: possible evidence of graft-versus-tumour effect. Intern Med J 2007; 37:127-9. [PMID: 17229257 DOI: 10.1111/j.1445-5994.2007.01244.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Mediastinal germ cell tumours (GCT) carry a poor prognosis, particularly after relapse. We have reviewed the published reports of current treatments and describe a case with a cure after an allogeneic bone marrow transplant, which is not reported in the current published data. We believe that GCT may be susceptible to a graft-versus-tumour effect and suggest that patients with relapsed GCT be considered for allogeneic transplantation.
Collapse
Affiliation(s)
- A Goodwin
- Westmead Hospital Medical Oncology Department, Westmead Hospital, Westmead, NSW, Australia.
| | | | | |
Collapse
|