☆Corrigendum to “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. 137 (2019) (May) 154–164]

379 Background: Testicular germ-cell cancer is curable even in the presence of metastatic disease. Yet, about 10-15% of patients become cisplatin-refractory and will eventually die of their disease. Moreover, short- and long-term side effects of cisplatin make the search for less toxic treatment strategies worthwile. Programmed Death Receptor 1 (PD-1, CD279) is one member of the extended family of T cell regulators expressed on the surface of activated T cells, B cells, and macrophages. Its ligand, PD-L1 (B7-H1, CD274), is expressed on tumor cells, T cells and other tissues. The interaction of these two molecules negatively regulates immune responses. Of major interest is that inhibition of the interaction between PD-1 and PD-L1 can enhance T-cell responses in vitro and mediate clinical antitumor activity . The aim of this study was to analyze the expression of PD-L1 in testicular germ-cell tumors to evaluate its potential as predictive marker for further therapeutic strategies. Methods: Immunohistochemistry was performed in 486 Formalin Fixed Paraffin Embedded (FFPE) specimens using a monoclonal rabbit antibody (E1L3N, Cell Signaling Technology, Inc. (CST) of Danvers, MA, USA). Results: PD-L1 expression was found in 171 out of 248 (69%) seminomas, 19 out of 48 (40%) yolk sac tumors, 7 out of 46 (15%) teratomas, 2 out of 10 (20%) choriocarcinomas and 53 out of 87 (61%) embryonal carcinomas. In 20 out of 20 Intratubular germ-cell neoplasia unclassified (IGCNU) and also in 20 out of 20 normal tissue specimens no single case exhibited PD-L1 expression. Conclusions: Our study describes for the first time the frequent expression of PD-L1 in a large series of human testicular germ-cell tumors, but not on normal testis tissue or IGCNU. Based on our results, checkpoint inhibition with anti-PD1 and anti-PDL1 antibodies might represent an attractive approach in germ-cell cancer, where new active agents are urgently needed.

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ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up

Annals of Oncology ◽

10.1093/annonc/mdy217 ◽

2018 ◽

Vol 29 (8) ◽

pp. 1658-1686 ◽

Cited By ~ 83

Author(s):

F. Honecker ◽

J. Aparicio ◽

D. Berney ◽

J. Beyer ◽

C. Bokemeyer ◽

...

Keyword(s):

Germ Cell ◽

Cancer Diagnosis ◽

Cell Cancer ◽

Consensus Conference ◽

Germ Cell Cancer ◽

Testicular Germ Cell ◽

Testicular Germ Cell Cancer

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Comparing diagnosis, management, and outcomes of synchronous versus metacrhonus brain metastases from testicular germ cell tumors (TGCT): Multinstitutional experience from the Spanish Germ Cell Cancer Group (SGCCG).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4560 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4560-4560

Author(s):

Jorge Aparicio ◽

Regina Girones ◽

Pere Roure ◽

Jose R. Germa-Lluch ◽

Sergio Vazquez-Estevez ◽

...

Keyword(s):

Brain Metastases ◽

Germ Cell ◽

Cell Cancer ◽

Germ Cell Tumors ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell ◽

Term Survival ◽

Cancer Group ◽

Group 2 ◽

Group 1

4560 Background: Metastases of testicular germ cell tumors (TGCT) to brain are a rare event. Prognostic is poor and there is little evidence on optimal management of these patients. Methods: A retrospective review of case records of germ cell tumor patients within the Spanish Germ Cell Cancer Group from 1994 to 2012 was conducted. Results: Thirty-tree cases of testicular germ cell tumors from 17 institutions were reported. Nineteen patients (57%) presented with brain metastases at primary diagnosis (group 1: synchronous), thirteen (40%) developed brain metastases at relapse (group 2: metachronous) and only one patient developed brain metastasis during cisplatin based-chemotherapy (3%) (excluded from the analysis). Main demographics and comparison between series are shown on table. Median serum BHCG levels at initial diagnosis were higher in group 1(279.083 versus 175.873), whereas those of AFP were higher in group 2(1320 versus 4181). The most common histology in the primary tumor was choriocarcinoma for group; versus embryonal carcinoma for group 2. Patients had neurological symptoms at diagnosis of brain metastases (63% synchronic/93% metachronus). Performance status was also poor (PS 2-3: 52,6%group 1-62,2% group 2). Four patients (21%) in group 1 had a solitary brain lesion vs seven (54%) on group 2. Median time since last dose of cisplatin to development of brain metastases on group 2 was 6 months (3-22).Median overall survival was 16 months (95% CI 5,3-26,6): group 1: 16 (95% CI 13,9-18);23 group 2 (95% CI 0-165). We have not found significant differences in survival between both groups. Overall 37,5% of patients achieved long-term survival (38,9% in group 1 versus 38,5% in group 2). Patients achieving complete response of brain metastases had a better survival (log rank p:0,003). Conclusions: Long term survival can be achieved in approximately 1/3 of patients with brain metastases. Chemotherapy remains the cornerstone of treatment. Selection bias because of the retrospective nature of review should make us be careful with the conclusions.

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Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.4.701 ◽

1994 ◽

Vol 12 (4) ◽

pp. 701-706 ◽

Cited By ~ 224

Author(s):

S Williams ◽

J A Blessing ◽

S Y Liao ◽

H Ball ◽

P Hanjani

Keyword(s):

Germ Cell ◽

Gynecologic Oncology ◽

Cell Cancer ◽

Germ Cell Tumors ◽

Germ Cell Cancer ◽

Gynecologic Oncology Group ◽

Long Term Follow Up ◽

Acute Myelomonocytic Leukemia

PURPOSE This study was performed to determine the effectiveness of postoperative adjuvant chemotherapy in patients with surgically resected ovarian germ cell tumors. PATIENTS AND METHODS After tumor removal and thorough surgical staging, patients were enrolled on this study and treated with three courses of cisplatin, etoposide, and bleomycin (BEP). Reassessment laparotomy was required of consenting, appropriate patients initially, but became an optional procedure in 1989. RESULTS Of 93 patients assessable on this trial, 89 are continuously free of germ cell cancer. At second-look laparotomy, two other patients were found to have small foci of immature teratoma; both remain clinically free of recurrence. One received subsequent alternate chemotherapy and one did not. Thus, 91 of 93 patients are currently free of germ cell cancer. Follow-up duration ranges from 4.0 to 90.3 months, with 67 patients monitored for longer than 2 years. Acute toxicity was moderate. One patient developed acute myelomonocytic leukemia 22 months after diagnosis. Another patient was noted to have a malignant lymphoma 69 months after protocol treatment. CONCLUSION Three courses of BEP will nearly always prevent recurrence in well-staged patients with completely resected ovarian germ cell tumors and should be given to all such patients. The development of acute leukemia as a complication of treatment is disturbing and mandates careful long-term follow-up, but is unusual and does not alter the risk-to-benefit ratio of treatment.

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Importance of a new tumor market TRA-1-60 in the follow-up of patients with clinical stage I nonseminomatous testicular germ cell tumors

Annals of Surgical Oncology ◽

10.1007/bf02303582 ◽

1997 ◽

Vol 4 (4) ◽

pp. 321-327 ◽

Cited By ~ 15

Author(s):

Mariël E. Gels ◽

Jan Marrink ◽

Petra Visser ◽

Dirk Th. Sleijfer ◽

Jos H. J. Droste ◽

...

Keyword(s):

Germ Cell ◽

Clinical Stage ◽

Germ Cell Tumors ◽

Stage I ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell

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Targeted serum miRNA (TSmiR) test for diagnosis and follow-up of (testicular) germ cell cancer patients: A proof of principle

Molecular Oncology ◽

10.1016/j.molonc.2013.08.002 ◽

2013 ◽

Vol 7 (6) ◽

pp. 1083-1092 ◽

Cited By ~ 85

Author(s):

Ad J.M. Gillis ◽

Martin A. Rijlaarsdam ◽

Ronak Eini ◽

Lambert C.J. Dorssers ◽

Katharina Biermann ◽

...

Keyword(s):

Germ Cell ◽

Cancer Patients ◽

Cell Cancer ◽

Germ Cell Cancer ◽

Testicular Germ Cell ◽

Serum Mirna ◽

Testicular Germ Cell Cancer ◽

Proof Of Principle

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Prognosis of anaemia in disseminated testicular germ cell tumours. On behalf of the Spanish Germ Cell Cancer Group (SGCCG)

Annals of Oncology ◽

10.1093/annonc/mdz249.080 ◽

2019 ◽

Vol 30 ◽

pp. v399

Author(s):

E. Garcia Torralba ◽

D. Castellano Gauna ◽

N. Sobrevilla ◽

J. Guma ◽

M.I. Luengo ◽

...

Keyword(s):

Germ Cell ◽

Cell Cancer ◽

Germ Cell Cancer ◽

Germ Cell Tumours ◽

Testicular Germ Cell ◽

Testicular Germ Cell Tumours ◽

Cancer Group

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Evaluation of Circulating miRNA Biomarkers of Testicular Germ Cell Tumors during Therapy and Follow-up―A Copenhagen Experience

Cancers ◽

10.3390/cancers12030759 ◽

2020 ◽

Vol 12 (3) ◽

pp. 759

Author(s):

Nina Mørup ◽

Ewa Rajpert-De Meyts ◽

Anders Juul ◽

Gedske Daugaard ◽

Kristian Almstrup

Keyword(s):

Germ Cell ◽

Tumor Markers ◽

Germ Cell Tumors ◽

Primary Diagnosis ◽

University Hospital ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell ◽

Circulating Mirna ◽

Serum Tumor Markers

New microRNA-based serum biomarkers (miRNA-367-3p, -371a-3p, -372-3p, and -373-3p) have shown great potential for the detection of testicular germ cell tumors (TGCTs), but few studies have investigated the clinical utility and performance of these tests in treatment monitoring. In this study, circulating miRNA levels were measured, together with serum tumor markers alpha-fetoprotein (AFP), β-subunit of human chorionic gonadotropin (β-HCG) and lactate dehydrogenase (LDH) in 406 consecutive blood samples obtained during the treatment and follow-up of 52 TGCT patients at the Copenhagen University Hospital. After testing three different methods of RNA isolation from peripheral blood and PCR quantification in a subset of samples (n = 15), the best performing setup of targeted isolation of miRNAs inside and outside exosomes was selected to analyze all samples. At primary diagnosis, the miRNAs significantly outperformed the serum tumor markers, with a sensitivity and specificity of 78% and 100% (based on 40 patients), respectively. The picture was not as clear when patient trajectories were investigated, with both positive and negative signals for miRNAs and serum tumor markers. To establish whether measuring miRNAs adds value beyond the primary diagnosis, large prospective clinical trials comparing miRNAs and classical tumor markers during the treatment and follow-up of TGCT patients are needed.

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