Germ Cell Tumor Patients Research Articles

Onco-Testicular Sperm Extraction (oncoTESE): A Contemporary Concept Review and Report of Australian Sperm Retrieval Rates and Fertility Outcomes

ObjectiveTo assess sperm retrieval rates of Onco-Testicular Sperm Extraction (oncoTESE) in men with testicular tumors and coexisting severe spermatogenic impairment. MethodsMulti-centre Australian wide retrospective review of oncoTESE procedures performed within the last 10 years. Patients were postpubertal adults having a testicular tumor requiring orchidectomy, with severe oligozoospermia or nonobstructive azoospermia. Ipsilateral testicular sperm extraction was performed following radical inguinal orchidectomy. A contralateral micro-testicular sperm extraction was performed if no sperm or insufficient amounts were initially achieved. Surgical sperm retrieval rates, live birth rates and post operative serum testosterone were recorded. ResultsFour surgeons compiled a total 13 patients. The mean age was 34.9 years. Seven of 13 were germ cell tumor (GCT), 4 of 13 had non-GCT and 2 of 13 contained benign lesions. Twelve of 13 patients were azoospermic and 1 was severely oligozoospermic. Sperm was found in 6 of 7 GCT patients; 3 of 7 were found in the ipsilateral testis whilst the remaining 4 underwent contralateral micro-testicular sperm extraction; sperm was retrieved in 3 of 4. The respective mean pre and post orchidectomy testosterone was 12.0 vs 14.1nmol/L (GCT cohort). Cryopreserved sperm has been used in assisted reproduction in 2 of 13 patients, with median follow up of 38.7 months. Including use of both cryopreserved and fresh sperm, 6 pregnancies were achieved, including 5 healthy live births and 1 miscarriage. ConclusionOncoTESE appears feasible, with acceptable sperm retrieval and subsequent live birth rates, following assisted reproduction. Despite significant underutilisation in the Australian population, oncoTESE should be considered in the management for TC patients with severe oligozoospermia, or nonobstructive azoospermia.

IMMU-49. DYNAMIC CHANGES AND PROGNOSTIC VALUE OF PERIPHERAL BLOOD LYMPHOCYTE SUBSETS IN INTRACRANIAL GERM CELL TUMORS

Abstract OBJECTIVE This study was designed to retrospectively analyze the dynamic changes of peripheral blood lymphocyte subsets and prognosis among patients with intracranial germ cell tumors. METHODS A total of 150 intracranial germ cell tumors patients diagnosed between June 2011 till November 2019 were retrospectively investigated. Peripheral blood total T lymphocytes (CD3+) percentage, T helper/inducible lymphocytes(CD3+CD4+)percentage, T inhibitory/toxic lymphocytes (CD3+CD8+) percentage, B lymphocyte (CD19+) percentage, NK lymphocyte (CD3/CD16+CD56+) percentage, regulatory T cells (CD4+CD25+,CD8+CD25+), and T helper/toxic lymphocyte ratio (CD4+/CD8+ ratio) were quantified by flow cytometry analysis. Clinical information was extracted from the database in Sun Yat-sen University Cancer Center and survival data was confirmed through outpatient visits and telephone follow-up. RESULTS T lymphocytes population was increased after anti-tumor treatment, with significant difference of total T lymphocytes (CD3+), inhibitory/toxic T cells (CD3+CD8+) and regulatory T cells (CD4+CD25+ and CD8+CD25+), (p=0.008, p=0.000, p=0.008 and p=0.001 respectively), while B lymphocytes(CD19+) decreased after chemotherapy(p=0.003). The dynamic levels of T lymphocyte and B lymphocyte subpopulation after chemotherapy did not present significant differences between gender, age, and locations of tumors (p >0.05), except CD4+CD25+ T cells in younger children (age< 16 years older) increased significantly than the elder (age >16), p=0.04. Patients with increased CD19+ B cells presented significant suboptimal outcomes compared with the no increased (p=0.024). Similarly, increased CD3+ T cells, CD3+CD8+ T cells, CD4+CD25+ T cells reduced the risk of death (p=0.006, p=0.019, p=0.042 respectively). Multivariate Cox Regression analysis showed: increased CD19+ B cells, p=0.04, HR=1.688, 95%CI=1.025-2.779. CONCLUSION After anti-tumor treatment, cell-mediated immunity activated, enhanced, and dominated in anti-tumor response. An increased level of CD19+ subsets was an independent predictor for inferior overall survival. Systemic circulating T cells immunity played an important role and mediating antitumor responses may pave the road for new immunity strategies.

\u201cChronic fatigue, quality of life and long-term side-effects of chemotherapy in patients treated for non-epithelial ovarian cancer: national case-control protocol study of the GINECO-Vivrovaire rare tumors INCa French network for rare malignant ovarian tumors\u201d

BackgroundGerm cell tumors and sex cord stromal tumors are rare cancers of the ovary. They mainly affect young women and are associated with a high survival rate. The standard treatment mainly involves conservative surgery combined with chemotherapy [bleomycin, etoposide and cisplatin (BEP)] depending on the stage and the prognostic factors, as for testicular cancers. As reported in testicular cancer survivors, chemotherapy may induce sequelae impacting quality of life, which has not yet been evaluated in survivors of germ cell tumors and sex cord stromal tumors. The GINECO-VIVROVAIRE-Rare tumor study is a two-step investigation aiming to assess i) chronic fatigue and quality of life and ii) long-term side-effects of chemotherapy with a focus on cardiovascular and pulmonary disorders.MethodsUsing self-reported questionnaires, chronic fatigue and quality of life are compared between 134 ovarian cancer survivors (cancer-free ≥2 years after treatment) treated with surgery and chemotherapy and 2 control groups (67 ovarian cancer survivors treated with surgery alone and 67 age-matched healthy women). Medical data are collected from patient records. In the second step evaluating the long-term side-effects of chemotherapy, a subgroup of 90 patients treated with chemotherapy and 45 controls undergo the following work-up: cardiovascular evaluation (clinical examination, non-invasive cardiovascular tests to explore heart disease, blood tests), pulmonary function testing, audiogram, metabolic and hormonal blood tests. Costs of sequelae will be also assessed. Patients are selected from the registry of the INCa French Network for Rare Malignant Ovarian Tumors, and healthy women by the ‘Seintinelles’ connected network (collaborative research platform).DiscussionThis study will provide important data on the potential long-term physical side-effects of chemotherapy in survivors of Germ Cell Tumors (GCT) and Sex Cord Stromal Tumors (SCST), especially cardiovascular and pulmonary disorders, and neurotoxicity. The identification of long-term side-effects can contribute to adjusting the treatment of ovarian GCT or SCST patients and to managing follow-up with adapted recommendations regarding practices and chemotherapy regimens, in order to reduce toxicity while maintaining efficacy. Based on the results, intervention strategies could be proposed to improve the management of these patients during their treatment and in the long term.Trial registrationThis trial was registered at clinicaltrials.gov: 03418844, on 1 February 2018.This trial was registered on 25 October 2017 under the unique European identification number (ID-RCB): 2017-A03028–45.Recruitment Status: Recruiting.Protocol versionVersion n° 4.2 dated from Feb 19, 2021.Trial sponsorCentre François Baclesse, 3 avenue du Général Harris, F-14076 Caen cedex 05, France.

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

Simple SummaryTesticular germ cell tumors are the most common solid cancers in men aged between 15–39 years. There is a need of non-invasive biomarkers for diagnosis and follow-up of these patients. miR-371a-3p has emerged as the most reliable biomarker of this disease, but fails to detect the teratoma subtype, which has clinical implications. In this work we describe a new method that combines miR-371a-3p quantification using RT-qPCR and hypermethylated RASSF1A quantification by droplet digital PCR in serum samples of these patients. The combination of both biomarkers detected disease (including teratoma) with a sensitivity of 100%, using cutoffs that made all healthy participants negative, being of interest for implementation in the clinical setting. 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.

Prophylaxis Against Thromboembolic Events During Chemotherapy for Germ Cell Cancer.

IntroductionPatients with advanced germ cell tumors (GCT) receiving cisplatin-based chemotherapy have high rates of thromboembolic events (TEE) which can negatively affect their overall survival. While primary TEE prophylaxis during chemotherapy may prevent these events, it is unclear which patients will benefit in this setting.Materials and MethodsA review of PubMed/Medline was conducted in December 2020 and all pertinent articles were evaluated for relevancy and quality of data for inclusion in the review.ResultsStudies on patients receiving initial cisplatin-based chemotherapy for advanced GCT have reported up to a 19% rate of TEE. This high rate may be associated with multiple factors including retroperitoneal lymphadenopathy, advanced clinical stage, high risk Khorana scores and presence of a central line. Large phase III clinical trials have demonstrated the benefit of low-molecular-weight-heparin and direct oral anticoagulants for primary prophylaxis and against recurrent TEE. However, primary prophylaxis is currently underutilized with GCT patients starting chemotherapy.ConclusionPrecise models to predict TEE risk and consideration of anticoagulation are difficult to develop owing to the relatively uncommon nature of GCT and lack of representation in primary TEE prophylaxis clinical trials. Despite these limitations, we believe that the benefits of prophylactic anticoagulation outweigh the risk of major bleeding in select GCT patients with higher risk of TEE. We have developed a simple algorithm to help guide TEE prophylaxis selection based on patient factors and route of chemotherapy administration. Given the high rate of TEE in GCT patients, we believe better utilization of primary prophylaxis in patient starting cisplatin-based chemotherapy will have clinical benefit.

Narrative review of developing new biomarkers for decision making in advanced testis cancer.

Management of testicular germ cell tumor (GCT) patients is based on clinical determinants, mainly CT scan and serum tumor markers (alpha-fetoprotein, beta subunit of HCG and LDH). Treatment decisions are usually straightforward for patients with clear evidence of metastatic disease, confirmed either by imaging tests or by unequivocal elevated tumor markers. However, there are several clinical scenarios where the assessment of metastatic disease is complicated by the limited specificity of the current imaging tests and serum tumor markers. These include patients with clinical stage IIA GCT with negative tumor markers and patients with post-chemotherapy residual disease where, in absence of clear indicators of GCT, decision making and patient treatment allocation become challenging. Therefore, more accurate biomarkers are critical to reduce the risk of under-or over-treatment and to always deliver the most optimal therapy. The objectives of this narrative review are to review the available publications about micro-RNAs in GCT s and their potential clinical applications. Two clusters of micro-RNAs, miR-371a-3p and miR-302/367, specifically expressed by both seminoma and non-seminoma GCT and easily detectable in the peripheral blood, have demonstrated to be promising in this endeavor. Large prospective trials are ongoing to define the operating characteristics of these biomarkers and their clinical utility to improve GCT patient management and reduce the error rate deriving from clinical uncertainty, therefore reducing the risk of sub-optimal treatments.

31. GENETIC CONTROL OF DECONVOLVED BRAIN CELL-TYPES

Choriocarcinoma germ cell tumors are rare and usually present with significantly elevated human chorionic gonadotropin (hCG) levels. When curable, it is felt to be largely a result of chemotherapy. We sought to determine the histologic characteristics for those undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and compare them with metastatic nonseminomatous germ cell tumor (NSGCT) patients with similarly elevated hCG levels.We reviewed medical records of men undergoing PC-RPLND between 1988 and 2017 with postorchiectomy, preinduction chemotherapy hCG levels greater than 50,000 mIU/ml. They were stratified by primary tumor histology: Pure choriocarcinoma and mixed NSGCT. Clinical, pathologic, and serologic data were reported and logistic regression was used to assess for predictors of necrosis in the PC-RPLND specimen.Our cohort consisted of 108 men. The mixed group (n = 91) had a median hCG of 165,177 mIU/ml, a postchemotherapy node size of 4.7 cm, of whom 19.8% also received salvage chemotherapy prior to RPLND. The pure choriocarcinoma group (n = 17) had a median hCG of 170,267 mIU/ml, a node size of 5.1 cm, of whom 17.6% received salvage chemotherapy. 88.2% of patients with choriocarcinoma had necrosis in the PC-RPLND specimen compared with 29.7% of the mixed NSGCT group (P = <0.0001). Controlling for salvage chemotherapy use, prechemotherapy hCG, node size and marker status, choriocarcinoma patients were 20 fold more likely to have necrosis on RPLND specimen (Odds ratio 20.68 [95% confidence interval 5.279–81.114]).While PC-RPLND is appropriate in patients with residual masses after chemotherapy, patients with pure choriocarcinoma presenting with significantly elevated hCG levels represent a unique patient population where necrosis is found more often than anticipated.

TU17. GENOME-WIDE ANALYSIS OF PSYCHOLOGICAL RESILIENCE

Choriocarcinoma germ cell tumors are rare and usually present with significantly elevated human chorionic gonadotropin (hCG) levels. When curable, it is felt to be largely a result of chemotherapy. We sought to determine the histologic characteristics for those undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and compare them with metastatic nonseminomatous germ cell tumor (NSGCT) patients with similarly elevated hCG levels.We reviewed medical records of men undergoing PC-RPLND between 1988 and 2017 with postorchiectomy, preinduction chemotherapy hCG levels greater than 50,000 mIU/ml. They were stratified by primary tumor histology: Pure choriocarcinoma and mixed NSGCT. Clinical, pathologic, and serologic data were reported and logistic regression was used to assess for predictors of necrosis in the PC-RPLND specimen.Our cohort consisted of 108 men. The mixed group (n = 91) had a median hCG of 165,177 mIU/ml, a postchemotherapy node size of 4.7 cm, of whom 19.8% also received salvage chemotherapy prior to RPLND. The pure choriocarcinoma group (n = 17) had a median hCG of 170,267 mIU/ml, a node size of 5.1 cm, of whom 17.6% received salvage chemotherapy. 88.2% of patients with choriocarcinoma had necrosis in the PC-RPLND specimen compared with 29.7% of the mixed NSGCT group (P = <0.0001). Controlling for salvage chemotherapy use, prechemotherapy hCG, node size and marker status, choriocarcinoma patients were 20 fold more likely to have necrosis on RPLND specimen (Odds ratio 20.68 [95% confidence interval 5.279–81.114]).While PC-RPLND is appropriate in patients with residual masses after chemotherapy, patients with pure choriocarcinoma presenting with significantly elevated hCG levels represent a unique patient population where necrosis is found more often than anticipated.

Paclitaxel, Ifosfamide, and Cisplatin in Patients with Poor-prognosis Disseminated Nonseminomatous Germ Cell Tumors with Unfavorable Serum Tumor Marker Decline After First Cycle of Chemotherapy. The GCT-SK-003 Phase II Trial

BackgroundGerm cell tumors represent highly curable disease even in metastatic stage. However, poor-risk patients with an unfavorable serum tumor marker (STM) decline after the first cycle of chemotherapy represent a subgroup with dismal prognosis, with approximately 50% cure rate using bleomycin, etoposide, and cisplatin (BEP). ObjectiveThe aim of this study was to determine the efficacy and safety of paclitaxel, ifosfamide, and cisplatin (TIP) in this patient population. Design, setting, and participantsThis was an open-labeled, nonrandomized, single-center phase II trial to study the efficacy and toxicity of TIP in the first-line treatment of germ cell tumor patients with an unfavorable decline of STMs. Nineteen patients with a poor prognosis according to the International Germ Cell Cancer Collaboration Group classification and an unfavorable STM decline after the first cycle of chemotherapy were included in this phase II study (NCT02414685). The treatment regimen consisted of paclitaxel 250 mg/m2 on day 1, ifosfamide 1200 mg/m2 on days 1–5, and cisplatin 20 mg/m2 on days 1–5, totally for four cycles. Outcome measurements and statistical analysisThe primary endpoint was complete response (CR) rate. An optimal Simon two-stage design was used with a type I error of 5% and study power of 80%. If fewer than six CRs to study therapy have been observed among the first 19 patients, the study was to be terminated. Results and limitationsA CR was achieved in four (21.1%) patients; therefore, the study was terminated in the first stage. A favorable response rate (CR or partial remission with negative tumor markers) was observed in 14 (78.9%) patients. At a median follow-up period of 35.2 mo (range, 5.6–62.1 mo), ten (52.6%) patients experienced disease progression and eight patients (42.1%) died. The 2-yr progression-free and overall survival was 41.2% (95% confidence interval [CI] 16.8–65.7) and 72.7% (95% CI 48.9–96.4), respectively. TIP was well tolerated, and no unexpected toxicity was observed. No informative biomarkers, including miR-371a-3p was identified. ConclusionsTreatment modification from the BEP to the TIP regimen in patients with an unfavorable STM decline after the first cycle of chemotherapy was not associated with improved outcome, and four cycles of BEP remain the standard treatment option in this patient population. Patient summaryPoor-risk patients with an unfavorable serum tumor marker decline after the first cycle of chemotherapy represent a subgroup with dismal prognosis, with an approximately 50% cure rate using bleomycin, etoposide, and cisplatin (BEP). Treatment modification from the BEP regimen to the paclitaxel, ifosfamide, and cisplatin regimen in patients with an unfavorable serum tumor marker decline after the first cycle of chemotherapy was not associated with improved outcome, and four cycles of BEP remain the standard treatment option in this patient population.

V11-02 ROBOTIC CAVECTOMY DURING ONCOLOGICAL SURGERY: TECHNICAL CONSIDERATIONS AND OUTCOMES

You have accessJournal of UrologyRenal Oncology II (V11)1 Sep 2021V11-02 ROBOTIC CAVECTOMY DURING ONCOLOGICAL SURGERY: TECHNICAL CONSIDERATIONS AND OUTCOMES Wesley Yip, David Ortega, Luis Medina, Alireza Ghoreifi, Nima Nassiri, Bishoy Hanna, Akbar Ashrafi, Matthew Winter, Inderbir Gill, and Hooman Djaladat Wesley YipWesley Yip More articles by this author , David OrtegaDavid Ortega More articles by this author , Luis MedinaLuis Medina More articles by this author , Alireza GhoreifiAlireza Ghoreifi More articles by this author , Nima NassiriNima Nassiri More articles by this author , Bishoy HannaBishoy Hanna More articles by this author , Akbar AshrafiAkbar Ashrafi More articles by this author , Matthew WinterMatthew Winter More articles by this author , Inderbir GillInderbir Gill More articles by this author , and Hooman DjaladatHooman Djaladat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002073.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: An increasing proportion of renal cell carcinoma (RCC) and germ cell tumor (GCT) surgeries are being performed with a robotic-assisted laparoscopic approach. In cases of tumor and/or thrombus infiltrating the inferior vena cava (IVC) wall, adherence to the IVC endothelium, or obliteration of the IVC lumen, infra or suprarenal cavectomy may be indicated. We present our robotic cavectomy case series to demonstrate its technical feasibility and short-term outcomes. METHODS: Four patients underwent robotic cavectomy, either as adjuvant surgery (retroperitoneal lymph node dissection or radical nephrectomy) or primary procedure. Indications included: 1) post-chemotherapy retroperitoneal GCT involving the IVC, 2, 3) right-sided RCC with IVC tumor thrombus (Levels II and III), and 4) recurrent IVC tumor thrombus after previous open right radical nephrectomy and IVC thrombectomy. The post-chemotherapy retroperitoneal GCT patient underwent an infrarenal robotic cavectomy, while the RCC patients underwent suprarenal robotic cavectomies. None underwent caval reconstruction. RESULTS: All four patients tolerated intraoperative IVC clamping and subsequent cavectomy. Peri and 90-day postoperative outcomes are presented in Table 1. No patients required hemodialysis. During follow-up, there were no complications, lower extremity edema, or renal function deterioration, although the Level III IVC thrombus patient developed lung and retroperitoneal recurrences 15 months after surgery, which are planned for immunotherapy. Short-term oncological data is presented in Table 2. CONCLUSIONS: To our knowledge, this is the first case series of robotic cavectomy. We demonstrate that it can be safely performed in selected patients at experienced centers with low morbidity and complication rates. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e857-e858 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wesley Yip More articles by this author David Ortega More articles by this author Luis Medina More articles by this author Alireza Ghoreifi More articles by this author Nima Nassiri More articles by this author Bishoy Hanna More articles by this author Akbar Ashrafi More articles by this author Matthew Winter More articles by this author Inderbir Gill More articles by this author Hooman Djaladat More articles by this author Expand All Advertisement Loading ...

Comparative Analyses of Liquid-Biopsy MicroRNA371a-3p Isolation Protocols for Serum and Plasma.

Simple SummaryThe active disease status of patients with a malignant germ cell tumor can be evaluated using detection of specific body-circulating microRNAs. However, various methods are reported to isolate and detect microRNAs from blood, possibly influencing the score as positive or negative. Here, we investigated two frequently used techniques for microRNA isolation from blood, either serum or plasma, to evaluate possible differences. These data are required to compare published studies and to select the best methods in the future. No effect of either starting with plasma or serum was found, indicating that both blood products can be used. The bead-based method was more stable and applicable on small blood volumes, whereas the total RNA method exhibited a higher sensitivity due to a larger starting volume. These results are important to develop the optimal method for the detection of microRNAs in blood to monitor malignant germ cell tumor patients in clinic practice.MicroRNAs (miRNAs) are short, non-coding RNAs involved in translation regulation. Dysregulation has been identified in cancer cells. miRNAs can be secreted and detectable in body fluids; therefore, they are potential liquid-biopsy biomarkers. The miR-371a-3 cluster members are an example, monitoring the presence of malignant germ cell tumors based on patient serum/plasma analyses. However, a large variety of isolation techniques on sample types (serum vs. plasma) are reported, hampering interstudy comparisons. Therefore, we analyzed the impact of using the miRNeasy Serum/Plasma Kit (cell-free total RNA purification) Qiagen extraction kit and the TaqMan anti-miRNA bead-capture procedure of ThermoFisher for miRNA isolation. Ten normal male matched serum and plasma samples and seventeen testicular germ cell tumor patient serum samples were investigated. The Qiagen kit requires a higher input volume (200 µL vs. 50 µL), resulting in higher sensitivity. Serum and plasma comparison demonstrated high similarity in miRNA levels. Titration experiments showed that the bead-capture procedure is superior in cases of lower starting volumes (<100 µL). This study highlights the strengths and limitations of two different isolation protocols, relevant for in vivo analysis with small starting volumes. In summary, miRNA detection levels results varied little between plasma and serum, whereas for low volumes the bead capture isolation method is preferable.

Are Changes in the Percentage of Specific Leukocyte Subpopulations Associated with Endogenous DNA Damage Levels in Testicular Cancer Patients?

Chemoresistance of germ cell tumors (GCTs) represents an intensively studied property of GCTs that is the result of a complicated multifactorial process. One of the driving factors in this process is the tumor microenvironment (TME). Intensive crosstalk between the DNA damage/DNA repair pathways and the TME has already been reported. This study aimed at evaluating the interplay between the immune TME and endogenous DNA damage levels in GCT patients. A cocultivation system consisting of peripheral blood mononuclear cells (PBMCs) from healthy donors and GCT cell lines was used in an in vitro study. The patient cohort included 74 chemotherapy-naïve GCT patients. Endogenous DNA damage levels were measured by comet assay. Immunophenotyping of leukocyte subpopulations was performed using flow cytometry. Statistical analysis included data assessing immunophenotypes, DNA damage levels and clinicopathological characteristics of enrolled patients. The DNA damage level in PBMCs cocultivated with cisplatin (CDDP)-resistant GCT cell lines was significantly higher than in PBMCs cocultivated with their sensitive counterparts. In GCT patients, endogenous DNA damage levels above the cutoff value were independently associated with increased percentages of natural killer cells, CD16-positive dendritic cells and regulatory T cells. The crosstalk between the endogenous DNA damage level and specific changes in the immune TME reflected in the blood of GCT patients was revealed. The obtained data contribute to a deeper understanding of ongoing interactions in the TME of GCTs.

The Enigmatic Role of TP53 in Germ Cell Tumours: Are We Missing Something?

The cure rate of germ cell tumours (GCTs) has significantly increased from the late 1970s since the introduction of cisplatin-based therapy, which to date remains the milestone for GCTs treatment. The exquisite cisplatin sensitivity has been mainly explained by the over-expression in GCTs of wild-type TP53 protein and the lack of TP53 somatic mutations; however, several other mechanisms seem to be involved, many of which remain still elusive. The findings about the role of TP53 in platinum-sensitivity and resistance, as well as the reported evidence of second cancers (SCs) in GCT patients treated only with surgery, suggesting a spectrum of cancer predisposing syndromes, highlight the need for a deepened understanding of the role of TP53 in GCTs. In the following report we explore the complex role of TP53 in GCTs cisplatin-sensitivity and resistance mechanisms, passing through several recent genomic studies, as well as its role in GCT patients with SCs, going through our experience of Center of reference for both GCTs and cancer predisposing syndromes.

Non-metastasised clincial stage I testicular germ cell tumours : Patient information, suitability and limitations of surveillance

Surveillance is the most frequently used treatment option in testicular germ cell tumour (TGCT) patients in nonmetastasised clinical stageI (cSI). Presentation of indications for surveillance, the process of individual patient's advice and the limitations of surveillance. An overview of the current literature is given, including basic research, systemic reviews and expert recommendations. Basic principles are illustrated by case reports. The risk of progression for cSI TGCT patients under surveillance is 5-30% for seminomas and 15-50% for nonseminomas. Surveillance is the preferred treatment option in seminoma and low-risk nonseminoma without lymphovascular invasion. Patients should be informed concerning the individual risk of progression, the possibilities of adjuvant therapy, side effects of adjuvant therapy, the kind of therapy in case of progression and the cure rate. Ahigh risk of progression, psychological issues and malcompliance are important limitations of surveillance. By thoroughly considering the limitations of surveillance, cSI TGCT patients can be safely treated with surveillance.

Performance characteristics of 18F-fluciclovine positron emission tomography/computed tomography prior to retroperitoneal lymph node dissection.

We aimed to determine whether anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) positron emission tomography/computed tomography (PET/CT) can accurately detect residual non-seminomatous germ cell tumor (NSGCT) prior to retroperitoneal lymph node dissection (RPLND). There is no reliable way to differentiate between fibrosis/necrosis, teratoma, and viable germ cell tumor in patients receiving post-chemotherapy RPLND. Functional imaging, including 18F-fludeoxyglucose (18F-FDG) PET/CT, has been disappointing. Due to the need for better imaging modalities, our prospective, pilot study aims to investigate the accuracy of 18F-fluciclovine PET/CT in detecting residual tumor prior to RPLND. From March 2018 to May 2019, 10 eligible patients underwent preoperative 18F-fluciclovine PET/CT prior to undergoing bilateral, full-template RPLND or excision of mass (for one re-do RPLND) in a prospective, phase 2 study. Correlation between 18F-fluciclovine PET/CT and RPLND pathology were evaluated on a per-patient level. A total of 10 patients (mean age 29±7.6 years) underwent 18F-fluciclovine PET/CT prior to surgery. Nine of 10 patients received chemotherapy prior to RPLND. Correlation between 18F-fluciclovine PET/CT and RPLND pathology was seen in 3/10 (30%) patients. Five of 10 patients (50%) with negative 18F-fluciclovine PET/CT were found to have residual disease/teratoma on RPLND. Compared to the reference standard of RPLND, 18F-fluciclovine PET/CT demonstrated 29% sensitivity and 33% specificity. No patients experienced any adverse events due to 18F-fluciclovine PET/CT. Despite a different mechanism of action from 18F-FDG, 18F-fluciclovine has low sensitivity and specificity for residual teratoma in the retroperitoneum.

Are serum levels of 25-hydroxy vitamin D reduced following orchiectomy in testicular cancer patients?

BackgroundThe testis represents one place where the progenitor of vitamin D is converted into its active form. Loss of one testis was suggested to result in reduced vitamin D serum levels. Vitamin D deficiency would represent a significant health problem in the long-term course of patients with testicular germ cell tumors (GCTs) since most of them survive. The purpose of this study was to look to the serum 25(OH)-Vitamin D (25OHD) levels in patients with GCTs before and after orchiectomy. A total of 177 GCT patients underwent measurements of serum 25OHD levels, thereof 83 with preoperative measurements and 94 with measurements at six particular time-points from immediate postoperatively to >24 months. Longitudinal assessments of 25OHD serum levels were performed in individual patients with repeated measurements. A second analysis involved patient cohorts with measurements at six postoperative time-points. Serum levels of patients were also compared with 2 control groups, one consisting of 84 patients with non-neoplastic testicular diseases and another with 237 patients with non-neoplastic urologic diseases. We also looked to associations of 25OHD levels with levels of testosterone, follicle stimulating hormone (FSH), age, histology of GCT and season. Descriptive statistical methods were employed to compare groups and to analyze changes over time.ResultsNormal serum levels of 25OHD were found in 21.7%, 23.1%, 20.2%, 21.9% in GCT patients preoperatively, after >2 years, in control group 1 and control group 2, respectively. Levels were significantly higher in spring and summer, but no association was found with other parameters. We found a significant transient decrease of 25OHD levels with a nadir at 6-12 months after orchiectomy and a recovery thereafter.ConclusionContrasting with previous studies we found no permanent reduction of serum 25OHD levels after orchiectomy but transient postoperative drop of 25OHD levels. There were no associations of 25OHD levels with age, and levels of testosterone or FSH. Our results may point to a particular role of the testis in vitamin D metabolism and may thus enhance the understanding of the diverse physiological roles of the testis.

High-dose Chemotherapy in Germ Cell Cancer Patients With Brain Metastases: Experience of an Expert Center.

Germ cell tumor (GCT) patients with brain metastases (BM) have a poor prognosis and high risk of treatment failure. Optimal therapies for these patients remain controversial. The aim of this study was to report the outcomes of all GCT patients with BM treated with high-dose chemotherapy (HDCT) in our French expert center for GCT. We carried out a retrospective study of 35 GCT patients with BM who were treated from 2003 to 2019 with HDCT, followed by infusions of autologous peripheral blood hematopoietic stem cells. The overall survival at 2 years was 36.9% (95% confidence interval, 19.7-54). The median overall survival was 12 months and the median progression-free survival was 8 months. No variables were associated with better survival in the univariable analysis. Among the 35 patients included in our study, 31 completed HDCT and 4 stopped treatments after mobilization. Eleven patients (11) showed favorable responses (complete, partial, or stable disease) to HDCT and 20 patients died of disease progression (17) or toxicities (3). Among the 11 patients with favorable responses to HDCT, 8 (72.7%) had metachronous BM, mostly isolated. The majority of these patients did not receive local treatment at diagnosis or at relapse. Together, our study reveals that GCT patients can experience long-term survival even in the presence of BM. Metachronous BM can also be cured with HDCT even in the absence of local treatment. Biological and radiologic responses to mobilization could be a predictor of favorable responses to HDCT.

Advanced germ cell tumor patients undergoing post-chemotherapy retroperitoneal lymph node dissection: Impact of residual teratoma on prognosis.

To evaluate the histologic findings and clinical outcomes of post-chemotherapy retroperitoneal lymph node dissection for advanced germ cell tumor. We analyzed the medical records of 66 patients who underwent post-chemotherapy retroperitoneal lymph node dissection between 2005 and 2019 at Tsukuba University Hospital. The proportions of necrosis, teratoma, and viable germ cell tumor in the specimens were 62.1%, 36.4%, and 1.5%, respectively. The 5-year progression-free and overall survival rates were 82.3% and 91.3%, respectively. The 5-year overall survival rate of patients with residual teratoma was significantly worse than that of patients with necrosis only (74.1% vs 100%). Overall, three patients died: one from cancer and two from teratoma with somatic-type malignancy. Of these, two patients relapsed after incomplete resection of residual teratoma. When limited to patients with completely resected teratoma, the 5-year overall survival rate was 91.7%, which did not differ from that for patients with necrosis only. Multivariate analysis showed that presence of teratoma in the primary site and decrease in retroperitoneal lymph node mass to less than 50% of the initial tumor size were independent factors for residual teratoma. However, the absence of these factors could not reliably predict necrosis only in retroperitoneal lymph node dissection specimens. In our series, 98% of post-chemotherapy retroperitoneal lymph node dissection pathology was either necrosis or teratoma, with viable germ cell tumor only found in 2% of patients. Residual teratoma was associated with poorer prognosis, especially in cases of incomplete resection.

Surveillance alone in stage I malignant ovarian germ cell tumors: a MITO (Multicenter Italian Trials in Ovarian cancer) prospective observational study

ObjectiveThe aim of this study was to analyze the oncological outcome of stage I malignant ovarian germ cell tumors patients included in the MITO-9 study to identify those who might...

Immunity to childhood vaccines following high dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) for germ cell tumors (GCT) with comparison to Hodgkin lymphoma (HL).

5017 Background: HDCT/ASCT represents a curative salvage treatment for patients with GCT but is rarely used for other solid tumors. Patients undergoing HDCT/ASCT for hematologic neoplasms require revaccination for their childhood immunizations. Whether this is necessary in patients with GCT is unknown. Methods: In this prospective longitudinal study, patients with GCT undergoing HDCT-ASCT from 11/2010 to 5/2018 had serologies for Measles, Mumps, Rubella, Diphtheria, Tetanus, Polio, and Varicella Zoster measured before HDCT and at 3, 6, and in a subset, 12+ months after the last HDCT with results at these timepoints compared using descriptive statistics. In addition, titer levels at ≥6 months post-transplant were matched 1:1 for age and gender with HL patients who underwent HDCT/ASCT during the same time period. Immunity was compared between cohorts using the Cochran-Mantel-Haenszel test. Results: Of 80 patients with GCT (median age 30, 84% nonseminoma), 91% received 3 sequential transplants and 68 had repeat titers at ≥6 months. Immunity at baseline was &gt;95% for Diphtheria, Tetanus and Polio and 89% for Varicella Zoster but lower for Measles (74%), Mumps (85%), and Rubella (83%) (Table). Compared to baseline, proportional immunity for all infections was similar at 3, 6, and 12 months post-transplant in the GCT population (≥6 months shown in Table). Matching resulted in 58 GCT-HL pairs. One-year immunity was numerically lower for most infections in the HL vs. GCT patients and significantly decreased for Measles and Rubella (Table). Conclusions: To our knowledge, this is the first study to assess vaccine titers following HDCT/ASCT for GCT. We demonstrate that HDCT/ASCT does not result in loss of immunity to childhood vaccines and that GCT patients retain protective titers more frequently than those with HL. However, 15-31% of GCT patients lack MMR immunity at baseline and at 1-year post-ASCT. Therefore, we recommend checking MMR titers at 1-year post-ASCT with revaccination of those lacking immunity. Titer evaluation and revaccination is not necessary for other childhood immunizations.[Table: see text]