scholarly journals Liquid Biopsies in the Clinical Management of Germ Cell Tumor Patients: State-of-the-Art and Future Directions

2021 ◽  
Vol 22 (5) ◽  
pp. 2654
Author(s):  
João Lobo ◽  
Ricardo Leão ◽  
Carmen Jerónimo ◽  
Rui Henrique
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Liquid Biopsy ◽  
Cell Tumor ◽  
Response To Therapy ◽  
Liquid Biopsies ◽  
Presumptive Diagnosis ◽  
Future Directions ◽  
Surgical Specimen

Liquid biopsies constitute a minimally invasive means of managing cancer patients, entailing early diagnosis, follow-up and prediction of response to therapy. Their use in the germ cell tumor field is invaluable since diagnostic tissue biopsies (which are invasive) are often not performed, and therefore only a presumptive diagnosis can be made, confirmed upon examination of the surgical specimen. Herein, we provide an overall review of the current liquid biopsy-based biomarkers of this disease, including the classical, routinely used serum tumor markers—the promising microRNAs rapidly approaching the introduction into clinical practice—but also cell-free DNA markers (including DNA methylation) and circulating tumor cells. Finally, and importantly, we also explore novel strategies and challenges for liquid biopsy markers and methodologies, providing a critical view of the future directions for liquid biopsy tests in this field, highlighting gaps and unanswered questions.

Extragonadal Germ Cell Tumors of the Mediastinum and Retroperitoneum: Results From an International Analysis

2002 ◽  
Vol 20 (7) ◽  
pp. 1864-1873 ◽  
Author(s):  
Carsten Bokemeyer ◽  
Craig R. Nichols ◽  
Jean-P. Droz ◽  
Hans-J. Schmoll ◽  
Alan Horwich ◽  
...  
Keyword(s):  
Survival Rate ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Germ Cell Tumors ◽  
Treatment Strategies ◽  
Cell Tumor ◽  
Primary Tumor Site ◽  
Primary Tumors ◽  
Platinum Based Chemotherapy

PURPOSE: To characterize the clinical and biologic features of extragonadal germ cell tumor (EGCT) and to determine the overall outcome with currently available treatment strategies.PATIENTS AND METHODS: Of an unselected population of 635 consecutive patients treated from 1975 through 1996 at 11 cancer centers, 341 patients (54%) had primary mediastinal EGCT, and 283 patients (45%) had retroperitoneal EGCT. Five hundred twenty-four patients (83%) had a nonseminomatous germ cell tumor (GCT), and 104 patients (16%) had a seminomatous histology.RESULTS: After platinum-based induction chemotherapy with or without secondary surgery, 141 patients (49%) with mediastinal nonseminomas (median follow-up, 19 months; range, 1 to 178 months) and 144 patients (63%) with retroperitoneal nonseminoma (median follow-up, 29 months; range, 1 to 203 months) are alive (P = .0006). In contrast, the overall survival rate for patients with a seminomatous EGCT is 88%, with no difference between patients with mediastinal or retroperitoneal tumor location (median follow-up, 49 months; range, 4 to 193 months; respective 70 months; range, 1 to 211 months). A significantly lower progression-free survival rate was found in seminoma patients treated with initial radiotherapy alone compared with chemotherapy. Nonseminomatous histology, presence of nonpulmonary visceral metastases, primary mediastinal GCT location, and elevated beta-human chorionic gonadotropin were independent prognostic factors for shorter survival. Hematologic malignancies (n = 17) occurred without exception in patients with primary mediastinal nonseminoma. Sixteen patients developed a metachronous testicular cancer despite the use of platinum-based chemotherapy.CONCLUSION: Whereas patients with pure seminomatous EGCT histology have a long-term chance of cure of almost 90% irrespective of the primary tumor site, 45% of patients with mediastinal nonseminomas are alive at 5 years. This outcome is clearly inferior compared with patients with nonseminomatous retroperitoneal primary tumors.

Metachronous mature teratoma in the corpus callosum occurring 12 years after a pineal germinoma

2008 ◽  
Vol 109 (1) ◽  
pp. 126-129 ◽  
Author(s):  
Yuuta Kamoshima ◽  
Yutaka Sawamura ◽  
Motoyuki Iwasaki ◽  
Yoshinobu Iwasaki ◽  
Kazuhiko Sugiyama
Keyword(s):  
Corpus Callosum ◽  
Mr Imaging ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Tumor Size ◽  
Mature Teratoma ◽  
Cell Tumor ◽  
Pineal Germinoma ◽  
Second Tumor

The authors report a metachronous germ cell tumor with different histological type occurring 12 years after resection of a pineal germinoma. Histological examination of the original tumor revealed germinoma without any other component of germ cell tumor, and the patient underwent chemotherapy followed by 24 Gy of localized irradiation. Twelve years later, follow-up MR imaging showed a round mass in the genu of the corpus callosum. Two courses of chemotherapy were administered, but the tumor size remained stable. A second operation was performed and this second tumor was completely removed. The histological diagnosis was mature teratoma. The second tumor was considered as a metachronous mature teratoma rather than a recurrence of the original germinoma. To the authors' knowledge, this combination of metachronous germ cell tumor has not previously been reported in the literature

scholarly journals Prediction of residual retroperitoneal mass histology after chemotherapy for metastatic nonseminomatous germ cell tumor: multivariate analysis of individual patient data from six study groups.

1995 ◽  
Vol 13 (5) ◽  
pp. 1177-1187 ◽  
Author(s):  
E W Steyerberg ◽  
H J Keizer ◽  
S D Fosså ◽  
D T Sleijfer ◽  
G C Toner ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Individual Patient Data ◽  
Mature Teratoma ◽  
Study Groups ◽  
Patient Data ◽  
Cell Tumor ◽  
Data Set ◽  
Nonseminomatous Germ Cell Tumor

PURPOSE To develop a statistical model that predicts the histology (necrosis, mature teratoma, or cancer) after chemotherapy for metastatic nonseminomatous germ cell tumor (NSGCT). PATIENTS AND METHODS An international data set was collected comprising individual patient data from six study groups. Logistic regression analysis was used to estimate the probability of necrosis and the ratio of cancer and mature teratoma. RESULTS Of 556 patients, 250 (45%) had necrosis at resection, 236 (42%) had mature teratoma, and 70 (13%) had cancer. Predictors of necrosis were the absence of teratoma elements in the primary tumor, prechemotherapy normal alfa-fetoprotein (AFP), normal human chorionic gonadotropin (HCG), and elevated lactate dehydrogenase (LDH) levels, a small prechemotherapy or postchemotherapy mass, and a large shrinkage of the mass during chemotherapy. Multivariate combination of predictors yielded reliable models (goodness-of-fit tests, P > .20), which discriminated necrosis well from other histologies (area under the receiver operating characteristic (ROC) curve, .84), but which discriminated cancer only reasonably from mature teratoma (area, .66). Internal and external validation confirmed these findings. CONCLUSION The validated models estimate with high accuracy the histology at resection, especially necrosis, based on well-known and readily available predictors. The predicted probabilities may help to choose between immediate resection of a residual mass or follow-up, taking into account the expected benefits and risks of resection, feasibility of frequent follow-up, the financial costs, and the patient's individual preferences.

scholarly journals Combining Hypermethylated RASSF1A Detection Using ddPCR with miR-371a-3p Testing: An Improved Panel of Liquid Biopsy Biomarkers for Testicular Germ Cell Tumor Patients

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5228
Author(s):  
João Lobo ◽  
Lieke M. J. van Zogchel ◽  
Mohammed G. Nuru ◽  
Ad J. M. Gillis ◽  
C. Ellen van der Schoot ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Residual Disease ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Adult Males ◽  
Serum Samples ◽  
Liquid Biopsies ◽  
Testicular Germ Cell

The classical serum tumor markers used routinely in the management of testicular germ cell tumor (TGCT) patients—alpha fetoprotein (AFP) and human chorionic gonadotropin (HCG)—show important limitations. miR-371a-3p is the most recent promising biomarker for TGCTs, but it is not sufficiently informative for detection of teratoma, which is therapeutically relevant. We aimed to test the feasibility of hypermethylated RASSF1A (RASSF1AM) detected in circulating cell-free DNA as a non-invasive diagnostic marker of testicular germ cell tumors, combined with miR-371a-3p. A total of 109 serum samples of patients and 29 sera of healthy young adult males were included, along with representative cell lines and tumor tissue samples. We describe a novel droplet digital polymerase chain reaction (ddPCR) method for quantitatively assessing RASSF1AM in liquid biopsies. Both miR-371a-3p (sensitivity = 85.7%) and RASSF1AM (sensitivity = 86.7%) outperformed the combination of AFP and HCG (sensitivity = 65.5%) for TGCT diagnosis. RASSF1AM detected 88% of teratomas. In this representative cohort, 14 cases were negative for miR-371a-3p, all of which were detected by RASSF1AM, resulting in a combined sensitivity of 100%. We have described a highly sensitive and specific panel of biomarkers for TGCT patients, to be validated in the context of patient follow-up and detection of minimal residual disease.

scholarly journals Metastatic germ cell tumor with complete response-7 years follow up

2017 ◽  
Vol 5 (12) ◽  
pp. 5443
Author(s):  
Branislava Golub Jakovljevic ◽  
Dejan Đokanović ◽  
Snježana Miličević ◽  
Anđa Škobić ◽  
Dejan Ćazić ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Germ Cell Tumors ◽  
Complete Response ◽  
Cell Tumor ◽  
Uncommon Disease ◽  
Malignant Germ Cell Tumors ◽  
Sites Of Metastases ◽  
Very High

Cancer of the testis is a relatively uncommon disease, accounting for approximately 1-1.5% of all cancers in males.  5% of the malignant germ cell tumors are made of extragonadal origin. Germ cell tumors occur in men younger, usually between 20 and 35 years old. We report a case of a patient with metastatic extragonadal germ cell tumor with multiple sites of metastases, and very high initial values of tumor marker human chorionic gonadotrophin (HCG)- 1351308. At the time of diagnosis, the patient was in a very poor general condition. After the applied chemotherapy, there was a complete response and 7 years later the patient is without any symptoms of disease.

High incidence of early metabolic syndrome in germ cell tumor: Report from a tertiary cancer center in India.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 488-488
Author(s):  
Bivas Biswas ◽  
Deepak Dabkara ◽  
Sandip Ganguly ◽  
Amit Dutt Dwary ◽  
Indranil Ghosh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Weight Gain ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Single Agent ◽  
Treatment Protocol ◽  
Cell Tumor ◽  
Platinum Based Chemotherapy

488 Background: Late metabolic syndrome is well known in survivors of testicular germ cell tumor (GCT). Literature about early metabolic syndrome is scarce. Methods: Single institutional review of testicular GCT between June’2011 and December’2014. Patients with minimum post-treatment follow-up of 6 months were screened for signs of metabolic syndrome as per National Cholesterol Education Program (NCEP), if they had recorded blood pressure ≥130/85 mm of Hg and/or ≥10% weight gain from baseline. Partial metabolic syndrome was defined as - at least one abnormal criteria as per NCEP. Results: Sixty-three patients of testicular GCT completed treatment and were eligible for evaluation. Twenty-five patients fulfilled the screening criteria with median follow-up of 15 months (range: 6-40); median age of 35 years (range: 24-65). Treatment protocol was combined platinum based chemotherapy in 68% (n=17/25), single agent carboplatin in 20% (n=5/25), and surveillance only in 12% (n=3/25). Complete metabolic syndrome was found in 36% (n=9/25), partial metabolic syndrome in 44% (n=11/25). Blood pressure ≥130/85 mm of Hg was found in 64% (n=16/25), serum triglyceride ≥1.7 mmol/L in 61% (n=14/23), serum HDL cholesterol <1 mmol/L in 76% (n=16/21), and fasting plasma glucose ≥5.6 mmol/L in 30% (n=6/20). Median weight gain was 5 Kg (range: 2-14). Conclusions: Features of early metabolic syndrome (complete or partial) were detected in 80% of testicular GCT survivors in symptomatic and screened patients, and also in those who were in surveillance or who received single agent carboplatin only. So, all testicular GCT survivors should be screened for early metabolic syndrome and early intervention should be initiated as it may have significant long-term effects on mortality and morbidity.

Localized testicular germ cell tumor surveillance: A Delphi consensus study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17060-e17060
Author(s):  
Angélique DA Silva ◽  
Aude Flechon ◽  
Stephane Culine ◽  
François Planchamp ◽  
Thibaut Murez ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Delphi Method ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Stage I ◽  
Chest Imaging ◽  
Testicular Germ Cell ◽  
Surveillance Practice

e17060 Background: Stage I testicular germ cell tumor (TGCT) has excellent cure rates and surveillance is fully included in patient’s management, particularly during the first years of follow-up. Surveillance guidelines differ between the scientific societies, with different recommendations concerning clinical and imaging frequency de-escalation and long term follow-up. We evaluated surveillance practice and schedules followed by French specialists and set up a DELPHI method to obtain a consensual surveillance program with an optimal schedule for patients with localized TGCT. Methods: An online survey on surveillance practice of stage I TGCT based on clinical-cases was conducted among urologists, radiotherapists and oncologists. Results were compared to AFU, ESMO and EAU guidelines. Then a panel of experts assessed surveillance proposals following a formal consensus method (DELPHI method). Statements were drafted after analysis of the previous survey and systematic literature review, with 2 successive rounds to reach a consensus. Results: Survey and DELPHI method were conducted between July 2018 and May 2019. 61 participated to the survey (69% oncologists, 15% urologists, 16% radiotherapists). About 65% of practitioners followed clinico-biological guidelines concerning 1 to 5 years of follow-up, only 25% discontinued surveillance after the 5th year, as recommended. No physician followed the ESMO guidelines of de-escalation chest imaging. A panel of 32 experts (78% oncologists, 16% urologists, 6% radiotherapists) was asked about 38 statements. Consensus was reached for 26 statements concerning clinico-biological surveillance modalities and end of surveillance after the 5th year of follow-up. For seminoma, abdominal ultrasound was proposed as an option to the abdominopelvic (AP) scan for the 4th year of follow-up. No consensus was reached regarding de-escalation of chest imaging. Conclusions: The survey proved that French TGCT specialists do not follow current guidelines. With DELPHI method, a consensus was obtained for frequency of clinico-biological surveillance, discontinuation of surveillance after the 5th year and discontinuation of AP scan on the 4th year of follow-up for seminoma. Questions remains concerning type and frequency of chest imaging.

Invasive germ-cell tumor detected by follow-up examination following orchiopexy for cryptorchidism

1995 ◽  
Vol 10 (5-6) ◽  
Author(s):  
J. Mayr ◽  
E. Breinl ◽  
M. Ratschek ◽  
W. Hechtl
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Cell Tumor

Update on Late Relapse of Germ Cell Tumor: A Clinical and Molecular Analysis

2003 ◽  
Vol 21 (1) ◽  
pp. 113-122 ◽  
Author(s):  
David W. George ◽  
Richard S. Foster ◽  
Robert A. Hromas ◽  
Kent A. Robertson ◽  
Gail H. Vance ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Initial Therapy ◽  
Cell Tumor ◽  
Late Relapse ◽  
Indiana University ◽  
Cytogenetic Analyses ◽  
Disease Free ◽  
Median Interval

Purpose: Analysis of patients with late relapse (LR) of germ cell tumor (GCT) with reports on clinical characteristics, outcomes, and molecular and cytogenetic features. Patients and Methods: Eighty-three patients evaluated at Indiana University from 1993 through 2000 for relapse of GCT more than 2 years from initial therapy were reviewed. Available specimens were investigated for expression of the transcription regulator FoxD3 and apurinic/apyrimidinic endonuclease and the presence of chromosome 12 abnormalities. Results: Median interval from initial presentation to LR was 85 months. Forty-three of 49 LR patients who underwent surgery were rendered disease free (NED), and 20 (46.5%) remain continuously NED. Thirty-two patients received chemotherapy, but only six (18.8%) obtained a complete remission. Five of these patients remain continuously NED after chemotherapy alone, including three who were chemotherapy naïve. Eighteen of these 32 patients were successfully rendered NED by postchemotherapy surgery, and 12 remain continuously NED. Two patients continue on observation with no treatment for their LR. Overall, 69 of the 81 treated patients (85.2%) ultimately achieved an NED state, and 38 (46.9%) remain continuously NED with median follow-up from LR therapy of 24.5 months (range, 1 to 83 months), whereas nine other patients are currently NED after therapy for subsequent relapses. Because of the small numbers of specimens tested, we were unable to draw any definitive conclusions from the molecular and cytogenetic analyses. Conclusion: GCT patients require lifetime follow-up. At the time of LR, surgical resection alone remains our preferred therapy.

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