scholarly journals State-of-the-Art Management of Germ Cell Tumors

2018 ◽  
pp. 319-323 ◽  
Author(s):  
Darren R. Feldman
Keyword(s):  
Germ Cell ◽  
State Of The Art ◽  
Early Stage ◽  
Germ Cell Tumors ◽  
High Stakes ◽  
Inappropriate Use ◽  
Common Mistake ◽  
Relative Rarity ◽  
Cure Rates ◽  
Perfect Storm

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.

scholarly journals ARID1A Regulates Transcription and the Epigenetic Landscape via POLE and DMAP1 While ARID1A Deficiency or Pharmacological Inhibition Sensitizes Germ Cell Tumor Cells to ATR Inhibition

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 905 ◽  
Author(s):  
Lukas Kurz ◽  
Alissa Miklyaeva ◽  
Margaretha A. Skowron ◽  
Nina Overbeck ◽  
Gereon Poschmann ◽  
...  
Keyword(s):  
Germ Cell ◽  
Dna Methyltransferase ◽  
Synthetic Lethality ◽  
Germ Cell Tumors ◽  
Epigenetic Landscape ◽  
Loss Of Function ◽  
Pharmacological Inhibition ◽  
Promising Target ◽  
Cure Rates ◽  
Tumor Types

Germ cell tumors (GCTs) are the most common solid malignancies found in young men. Although they generally have high cure rates, metastases, resistance to cisplatin-based therapy, and late toxicities still represent a lethal threat, arguing for the need of new therapeutic options. In a previous study, we identified downregulation of the chromatin-remodeling SWI/SNF complex member ARID1A as a key event in the mode of action of the histone deacetylase inhibitor romidepsin. Additionally, the loss-of-function mutations re-sensitize different tumor types to various drugs, like EZH2-, PARP-, HDAC-, HSP90- or ATR-inhibitors. Thus, ARID1A presents as a promising target for synthetic lethality and combination therapy. In this study, we deciphered the molecular function of ARID1A and screened for the potential of two pharmacological ARID1A inhibitors as a new therapeutic strategy to treat GCTs. By CRISPR/Cas9, we generated ARID1A-deficient GCT cells and demonstrate by mass spectrometry that ARID1A is putatively involved in regulating transcription, DNA repair and the epigenetic landscape via DNA Polymerase POLE and the DNA methyltransferase 1-associated protein DMAP1. Additionally, ARID1A/ARID1A deficiency or pharmacological inhibition increased the efficacy of romidepsin and considerably sensitized GCT cells, including cisplatin-resistant subclones, towards ATR inhibition. Thus, targeting ARID1A in combination with romidepsin and ATR inhibitors presents as a new putative option to treat GCTs.

scholarly journals Is Omentectomy Mandatory Among Early Stage (I, II) Malignant Ovarian Germ Cell Tumor Patients? A Retrospective Study of 223 Cases

2017 ◽  
Vol 27 (7) ◽  
pp. 1373-1378 ◽  
Author(s):  
Wenyan Xu ◽  
Yanfang Li
Keyword(s):  
Germ Cell ◽  
Early Stage ◽  
Survival Rates ◽  
Germ Cell Tumors ◽  
Stage I ◽  
Stage Ii ◽  
Histological Subtypes ◽  
Histologic Subtype ◽  
Gynecology And Obstetrics ◽  
Initial Surgery

ObjectiveThe aim of the study was to investigate whether omentectomy (OMT) is necessary in the operation for apparently early stage malignant ovarian germ cell tumors (MOGCTs).Methods and MaterialsSearching medical records database of Sun Yat-sen University Cancer Center from January 1, 1966, to November 30, 2015, patients with MOGCTs were identified and their age, year of diagnosis, tumor grade, histologic subtype, International Federation of Gynecology and Obstetrics stage, nodal findings, gross observation of omentum, and performance of OMT were assessed. Overall survivals of patients with or without OMT were compared using Kaplan-Meier survival curves.ResultsA total of 223 MOGCT cases with clinically early stage (stage I and II) disease and with the 3 common histological subtypes of MOGCT were obtained, which include yolk sac tumor (YST), dysgerminoma (DSG), and immature teratoma (IMT). There were 192 stage I cases and 31 stage II cases. Fifty-four patients were diagnosed with YST, 61 with DSG, and 108 with IMT. Omentectomy was performed as part of the initial surgery in 74.0% patients (165/223) and was omitted in 26.0% patients (58/223). Chemotherapy was administered in 88.3% (197/223) of all patients. The median follow-up was 82.0 months. The 10-year overall survival rates of the patients with and without OMT were 90.5% and 98.1%, respectively (P = 0.156). Regarding different stages or histological subtypes, the 10-year survival rates of the 2 groups were 92.0% versus 97.9% (P = 0.324, stage I), 83.2% versus 100% (P = 0.351, stage II), 89.2% versus 100% (P = 0.303, YST), 94.1% versus 100% (P = 0.470, DSG), and 89.4% versus 96.0% (P = 0.405, IMT), respectively.ConclusionsIn conclusion, OMT in patients with clinically early stage MOGCT may not improve patient survival and may be omitted.

scholarly journals Are omentectomy and lymphadenectomy necessary in patients with apparently early-stage malignant ovarian germ cell tumors?

2019 ◽  
Vol 29 (2) ◽  
pp. 398-403 ◽  
Author(s):  
Beijiao Qin ◽  
Wenyan Xu ◽  
Yanfang Li
Keyword(s):  
Prognostic Factors ◽  
Germ Cell ◽  
Early Stage ◽  
Survival Rates ◽  
Germ Cell Tumors ◽  
Yolk Sac ◽  
Immature Teratoma ◽  
Yolk Sac Tumor ◽  
Cancer Center ◽  
Early Stage Disease

ObjectiveTo evaluate the role of omentectomy and lymphadenectomy in the treatment of clinically apparent early-stage malignant ovarian germ cell tumors.MethodsWe retrospectively reviewed 245 patients with malignant ovarian germ cell tumors (yolk sac tumor, dysgerminoma, and immature teratoma) and with clinically early-stage disease, who were treated at Sun Yat-sen University Cancer Center between January 1, 1970 and December 31, 2017. The survival of patients who underwent either omentectomy or lymphadenectomy, or both (omentectomy/lymphadenectomy group) was compared with that of patients who did not undergo omentectomy or lymphadenectomy (non-omentectomy/lymphadenectomy group).ResultsSixty patients were diagnosed with yolk sac tumor, 74 with dysgerminoma, and 111 with immature teratoma. Of these 245 patients, 216 patients had stage I disease, 28 patients had stage II, and 1 patient had stage IIIA. There were 190 patients who underwent omentectomy and/or lymphadenectomy and 55 patients in the non-omentectomy/lymphadenectomy group, respectively. In the omentectomy/lymphadenectomy group, 112 patients underwent both omentectomy and lymphadenectomy, 71 underwent omentectomy only, and 7 underwent lymphadenectomy only. Two hundred and fourteen of 245 patients (87.3%) received post-operative chemotherapy. Median follow-up was 73 months (range 1–388). The 10-year overall survival rates in the omentectomy/lymphadenectomy group and non-omentectomy/lymphadenectomy groups were 96.8% and 100%, respectively (p=0.340). Multivariate analysis evaluating all potential prognostic factors showed that omentectomy and lymphadenectomy are not prognostic factors for survival.ConclusionsOmentectomy and lymphadenectomy do not appear to improve survival and may be omitted in patients with clinically apparent early-stage malignant ovarian germ cell tumors.

Bilateral Germ Cell Tumors Involving the Basal Ganglia and Thalamus

Neurosurgery ◽  
1989 ◽  
Vol 24 (4) ◽  
pp. 579-583 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Jun Yoshida ◽  
Yoshihisa Kida
Keyword(s):  
Basal Ganglia ◽  
Germ Cell ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Early Stage ◽  
Germ Cell Tumors ◽  
Biological Behavior ◽  
Computed Tomographic ◽  
Normal Limits ◽  
Extrapyramidal Signs

ABSTRACT Two cases of a human chorionic gonadotropin-producing germ cell tumor originating bilaterally in the basal ganglia and thalamus are reported. The biological behavior and clinical characteristics were similar to those of unilateral germinomas involving the basal ganglia and thalamus. Common clinical features were slowly progressive unilateral pyramidal signs and bilateral and/or unilateral extrapyramidal signs which occurred either concomitantly or sequentially. Bilateral symmetrical lesions were demonstrated by computed tomography and/or magnetic resonance imaging at an early stage of illness. Serum and cerebrospinal fluid human chorionic gonadotropin levels were elevated (116 and 141 mIU/ml, respectively) but decreased and remained within normal limits after radiation therapy alone. Radiosensitivity was confirmed by repeated computed tomographic scans and tumor marker measurements. Multiple concomitant germ cell tumors is a rare, but interesting lesion, especially considering its pathogenesis and oncogenesis.

Gynecologic Cancer Intergroup (GCIG) Consensus Review for Ovarian Germ Cell Tumors

2014 ◽  
Vol 24 (Supp 3) ◽  
pp. S48-S54 ◽  
Author(s):  
Jubilee Brown ◽  
Michael Friedlander ◽  
Floor J. Backes ◽  
Philipp Harter ◽  
Dennis M. O’Connor ◽  
...  
Keyword(s):  
Germ Cell ◽  
Early Stage ◽  
Gynecologic Cancer ◽  
Tumor Biology ◽  
Germ Cell Tumors ◽  
Clinical Trial Design ◽  
Cooperative Groups ◽  
Stage Disease ◽  
Fertility Sparing ◽  
Collaborative Efforts

AbstractMost women diagnosed with malignant ovarian germ cell tumors have curable disease and experience excellent survival with manageable treatment-associated morbidity, related both to tumor biology and improvements in treatment over the last 4 decades. Malignant ovarian germ cell tumors occur predominantly in girls, adolescents, and young women and are often unilateral tumors of early stage, although advanced-stage disease occurs in approximately 30% of patients. Tumors are usually chemosensitive, thereby allowing fertility-sparing surgery in most women with high chance of cure. Differences in practice do exist among providers in various subspecialties and geographic areas. In most settings, collaborative efforts among specialties allow the optimal treatment of women with these rare tumors, and implementation of standard guidelines at an international level should translate to effective clinical trial design, rapid accrual to clinical trials, and universally improved patient outcomes.This consensus guideline represents a summary of recommendations for diagnosis and management that has been agreed upon by cooperative groups worldwide. It builds upon individual publications including previously published summary documents and provides the most current practice standards validated worldwide.

State of the Art and Controversies in the Treatment of Testis Germ-Cell Tumors (TGT)

2009 ◽  
Vol 76 (4) ◽  
pp. 221-229
Author(s):  
R. Salvioni ◽  
N. Nicolai ◽  
A. Necchi ◽  
T. Torelli ◽  
L. Piva ◽  
...  
Keyword(s):  
Germ Cell ◽  
State Of The Art ◽  
Germ Cell Tumors

scholarly journals State-of-the-art approach in selective curable tumors: germ cell tumors

2008 ◽  
Vol 19 ◽  
pp. vii161-vii165
Author(s):  
G. Rustin ◽  
F. Rehman
Keyword(s):  
Germ Cell ◽  
State Of The Art ◽  
Germ Cell Tumors
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