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BioMed Research International 2014Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ... (Review)
Review
Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. A known complication of cisplatin administration is acute kidney injury (AKI). The nephrotoxic effect of cisplatin is cumulative and dose-dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI may result in chronic kidney disease. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney. There is predominantly acute tubular necrosis and also apoptosis in the proximal tubules. There is activation of multiple proinflammatory cytokines and infiltration of inflammatory cells in the kidney. Inhibition of the proinflammatory cytokines TNF-α or IL-33 or depletion of CD4+ T cells or mast cells protects against cisplatin-induced AKI. Cisplatin also causes endothelial cell injury. An understanding of the pathogenesis of cisplatin-induced AKI is important for the development of adjunctive therapies to prevent AKI, to lessen the need for dose decrease or drug withdrawal, and to lessen patient morbidity and mortality.
Topics: Acute Kidney Injury; Antineoplastic Agents; Cisplatin; Female; Humans; Interleukin-33; Interleukins; Kidney Tubules, Proximal; Male; Neoplasms, Germ Cell and Embryonal; Oxidative Stress; Tumor Necrosis Factor-alpha
PubMed: 25165721
DOI: 10.1155/2014/967826 -
Annals of Oncology : Official Journal... Aug 2019Since the update of the 4th edition of the WHO Classification of Central Nervous System (CNS) Tumors published in 2016, particular molecular characteristics are part of... (Review)
Review
Since the update of the 4th edition of the WHO Classification of Central Nervous System (CNS) Tumors published in 2016, particular molecular characteristics are part of the definition of a subset of these neoplasms. This combined 'histo-molecular' approach allows for a much more precise diagnosis of especially diffuse gliomas and embryonal CNS tumors. This review provides an update of the most important diagnostic and prognostic markers for state-of-the-art diagnosis of primary CNS tumors. Defining molecular markers for diffuse gliomas are IDH1/IDH2 mutations, 1p/19q codeletion and mutations in histone H3 genes. Medulloblastomas, the most frequent embryonal CNS tumors, are divided into four molecularly defined groups according to the WHO 2016 Classification: wingless/integrated (WNT) signaling pathway activated, sonic hedgehog (SHH) signaling pathway activated and tumor protein p53 gene (TP53)-mutant, SHH-activated and TP53-wildtype, and non-WNT/non-SHH-activated. Molecular characteristics are also important for the diagnosis of several other CNS tumors, such as RELA fusion-positive subtype of ependymoma, atypical teratoid rhabdoid tumor (AT/RT), embryonal tumor with multilayered rosettes, and solitary fibrous tumor/hemangiopericytoma. Immunohistochemistry is a helpful alternative for further molecular characterization of several of these tumors. Additionally, genome-wide methylation profiling is a very promising new tool in CNS tumor diagnostics. Much progress has thus been made by translating the most relevant molecular knowledge into a more precise clinical diagnosis of CNS tumors. Hopefully, this will enable more specific and more effective therapeutic approaches for the patients suffering from these tumors.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Brain; Brain Neoplasms; DNA Methylation; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Glioma; Humans; Immunohistochemistry; Molecular Targeted Therapy; Mutation; Neoplasms, Germ Cell and Embryonal; Prognosis; Survival Rate; Treatment Outcome
PubMed: 31124566
DOI: 10.1093/annonc/mdz164 -
Annals of Oncology : Official Journal... Oct 2018
Topics: Aftercare; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Europe; Female; Humans; Incidence; Long-Term Care; Medical Oncology; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Ovariectomy; Ovary; Societies, Medical; Survivorship; Treatment Outcome
PubMed: 29697741
DOI: 10.1093/annonc/mdy001 -
The Lancet. Oncology Apr 2016Management of paediatric extracranial germ-cell tumours carries a unique set of challenges. Germ-cell tumours are a heterogeneous group of neoplasms that present across... (Review)
Review
Management of paediatric extracranial germ-cell tumours carries a unique set of challenges. Germ-cell tumours are a heterogeneous group of neoplasms that present across a wide age range and vary in site, histology, and clinical behaviour. Patients with germ-cell tumours are managed by a diverse array of specialists. Thus, staging, risk stratification, and treatment approaches for germ-cell tumours have evolved disparately along several trajectories. Paediatric germ-cell tumours differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate, evidence-based care. Suboptimal outcomes remain for several groups of patients, including adolescents, and patients with extragonadal tumours, high tumour markers at diagnosis, or platinum-resistant disease. Survivors have significant long-term toxicities. The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into improved patient outcomes. Future trials will be characterised by improved risk-stratification systems, biomarkers for response and toxic effects, rational reduction of therapy for low-risk patients and novel approaches for poor-risk patients, and improved international collaboration across paediatric and adult cooperative research groups.
Topics: Adolescent; Adult; Biomarkers, Tumor; Child; Female; Humans; Male; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Pediatrics; Survivors; Testicular Neoplasms
PubMed: 27300675
DOI: 10.1016/S1470-2045(15)00545-8 -
International Journal of Molecular... May 2023Spermatocytic tumor (ST) is a very rare disease, accounting for approximately 1% of testicular cancers. Previously classified as spermatocytic seminoma, it is currently... (Review)
Review
Spermatocytic tumor (ST) is a very rare disease, accounting for approximately 1% of testicular cancers. Previously classified as spermatocytic seminoma, it is currently classified within the non-germ neoplasia in-situ-derived tumors and has different clinical-pathologic features when compared with other forms of germ cell tumors (GCTs). A web-based search of MEDLINE/PubMed library data was performed in order to identify pertinent articles. In the vast majority of cases, STs are diagnosed at stage I and carry a very good prognosis. The treatment of choice is orchiectomy alone. Nevertheless, there are two rare variants of STs having very aggressive behavior, namely anaplastic ST and ST with sarcomatous transformation, that are resistant to systemic treatments and their prognosis is very poor. We have summarized all the epidemiological, pathological and clinical features available in the literature regarding STs that have to be considered as a specific entity compared to other germ GCTs, including seminoma. With the aim of improving the knowledge of this rare disease, an international registry is required.
Topics: Male; Humans; Seminoma; Rare Diseases; Testicular Neoplasms; Orchiectomy; Sarcoma; Neoplasms, Germ Cell and Embryonal
PubMed: 37298487
DOI: 10.3390/ijms24119529 -
BMJ Clinical Evidence Jan 2016More than half of painless solid swellings of the body of the testis are malignant, with a peak incidence in men aged 30 to 34 years. Most testicular cancers are germ... (Review)
Review
INTRODUCTION
More than half of painless solid swellings of the body of the testis are malignant, with a peak incidence in men aged 30 to 34 years. Most testicular cancers are germ cell tumours and half of these are seminomas, which tend to affect older men and have a good prognosis.
METHODS AND OUTCOMES
We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of treatments following orchidectomy in men diagnosed with stage 1 germ cell tumours (confined to testis)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
RESULTS
At this update, 76 records were screened for inclusion. Appraisal of titles and abstracts led to the exclusion of 47 studies and the further review of 29 full publications. Of the 29 full articles evaluated, two systematic reviews and one RCT, were added at this update. Data from long-term follow-up of an already reported study were also added. We performed a GRADE evaluation for seven PICO combinations.
CONCLUSIONS
In this systematic overview, we categorised the efficacy for seven interventions based on information about the effectiveness and safety of adjuvant chemotherapy (including different drugs and the number of cycles), adjuvant radiotherapy (including different regimens), adjuvant surgery, and surveillance/observation.
Topics: Chemotherapy, Adjuvant; Humans; Male; Neoplasms, Germ Cell and Embryonal; Radiotherapy, Adjuvant; Testicular Neoplasms
PubMed: 26741128
DOI: No ID Found -
International Journal of Environmental... Jun 2023Nonepithelial ovarian cancers (NEOC) are a group of rare malignancies, including germ cell tumours (GCT) and sex cord-stromal tumours (SCST), along with small-cell... (Review)
Review
Nonepithelial ovarian cancers (NEOC) are a group of rare malignancies, including germ cell tumours (GCT) and sex cord-stromal tumours (SCST), along with small-cell carcinomas and sarcomas. GCTs represent 2-5% of ovarian cancers, with a yearly incidence of 4:100,000, and they usually affect young women and adolescents. Precursory germ cells of the ovary form the basis of GCT. They are histologically classified into primitive GCT, teratomas, and monodermal and somatic-type tumours associated with dermoid cysts. A primitive GCT can be either a yolk sac tumour (YST), dysgerminoma, or mixed germ cell neoplasm. Teratomas are either mature (benign) or immature (malignant). Given that malignant GCTs occur rarely compared to epithelial ovarian tumours (EOC), greater focus is required in their diagnosis and treatment. In this article, we review the epidemiology, clinical manifestations, diagnosis, and molecular biology, along with the management and therapeutic challenges.
Topics: Adolescent; Humans; Female; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Teratoma
PubMed: 37372675
DOI: 10.3390/ijerph20126089 -
American Society of Clinical Oncology... May 2018The state of the art management of germ cell tumors (GCT) in 2018 does not include novel agents targeting genomic alterations or exciting immunologic-based approaches... (Review)
Review
The state of the art management of germ cell tumors (GCT) in 2018 does not include novel agents targeting genomic alterations or exciting immunologic-based approaches but rather the avoidance of pitfalls in everyday practice. The relative rarity of GCT and high curability with correct management create the "perfect storm" for high-stakes errors to occur. This review focuses on several common pitfalls that should be avoided in staging and management of early-stage and advanced GCT in order to maximize patient outcomes. A particularly frequent misstep is to base treatment decisions on pre- rather than postorchiectomy tumor markers that, depending on marker directionality, can lead to either undertreatment with potentially inferior outcomes or overtreatment with excess toxicity. Another common mistake is the failure to consider the unique ability of GCT to differentiate and the distinct biology of teratoma (chemoresistance and lack of increased glucose uptake compared with normal tissue), which exerts a pervasive influence on nonseminoma management. This may lead to inappropriate use of PET scan to evaluate the postchemotherapy residual mass and, if negative, the conclusion that surgery is not needed whereas (FDG-negative) teratoma should be removed. It could also result in administration of additional unnecessary chemotherapy to patients with marker normalization but without robust radiographic response after 3 to 4 cycles of BEP. Finally, oncologists should strive to maintain standard chemotherapy doses, not substitute carboplatin for cisplatin, and refer to expert centers when expertise (e.g., RPLND) is not available locally in order to achieve optimal cure rates in advanced disease.
Topics: Biomarkers, Tumor; Combined Modality Therapy; Disease Management; Humans; Neoplasm Metastasis; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Treatment Outcome
PubMed: 30231334
DOI: 10.1200/EDBK_201139 -
American Society of Clinical Oncology... May 2018Over the past 5 decades, the use of well-validated, guideline-based strategies has resulted in high cure rates in newly diagnosed patients with germ cell cancer.... (Review)
Review
Over the past 5 decades, the use of well-validated, guideline-based strategies has resulted in high cure rates in newly diagnosed patients with germ cell cancer. However, about 30% of those with metastatic disease at initial presentation will experience refractory disease. Salvage treatment is far more complex and less validated than first-line treatment because it is rare, patient cohorts are more heterogeneous, and prognostic factors seem to have greater impact. Prior to the initiation of any salvage treatment, several considerations must be made, including assessment of known prognostic factors and choice of the optimal salvage strategy. Evaluation of patients according to their disease biology, response to prior treatment, and the extent of their tumor burden at the time of salvage treatment is crucial for establishing the optimal salvage strategy. Patients with metastatic germ cell cancer in whom adequate cisplatin-based first-line chemotherapy fails should be included in the ongoing randomized TIGER trial comparing conventional-dose chemotherapy with high-dose chemotherapy as first salvage treatment. Outside this trial, patients may be treated with conventional or high-dose chemotherapy depending on the presence or absence of adverse prognostic factors, availability of resources, and patient and physician preferences.
Topics: Combined Modality Therapy; Disease Management; Disease Progression; Drug Resistance, Neoplasm; Humans; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Prognosis; Recurrence; Retreatment; Treatment Outcome
PubMed: 30231348
DOI: 10.1200/EDBK_201189 -
Annals of Thoracic and Cardiovascular... Dec 2019Germ cell tumors (GCTs) are the most common malignancy among young men in the United States. Although prognosis is favorable and response to cisplatin-based chemotherapy... (Review)
Review
Germ cell tumors (GCTs) are the most common malignancy among young men in the United States. Although prognosis is favorable and response to cisplatin-based chemotherapy regimens is good, 10%-20% of patients with thoracic metastases require surgical management following completion of chemotherapy. Pulmonary metastasectomy (PM) has been employed for GCT patients with lung metastases for several decades. Outcomes have been excellent thus far. However, there have been no randomized controlled trials of PM in GCT and, as new surgical techniques are developed, there is variability in management. This article reviews the existing data on current management of pulmonary metastases in GCT, with attention paid to timing of surgery, surgical approaches, and complications.
Topics: Humans; Lung Neoplasms; Male; Metastasectomy; Neoplasms, Germ Cell and Embryonal; Pneumonectomy; Postoperative Complications; Risk Factors; Treatment Outcome
PubMed: 31723083
DOI: 10.5761/atcs.ra.19-00070