Treatment Of Germ Cell Tumors Research Articles

Difficulties in the diagnosis and treatment of germ cell tumors based on a clinical case

Germ cell tumors (GCT) are a group of rare malignant neoplasms. At the same time, the group of patients with this pathology is mainly young people aged 25–35 years. Taking into account the rarity of the disease and the young age of patients, there may often be difficulties in diagnostics and treatment of this malignant tumor. On the example of the described clinical case of a patient with seminomatous GCT the most frequent problems that specialists may encounter in the treatment of this pathology are presented.

Association between glutathione S-transferases M1 expression and treatment outcome in germ cell tumor patients.

Cisplatin-based chemotherapy is the mainstay in the treatment of germ cell tumors (GCTs). Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by chemotherapy and are thus implicated in developing treatment resistance. This study aimed to assess the expression level of GST mu 1 (GSTM1) and its association with treatment outcomes in patients with GCT. This translational study included tumor specimens from 207 patients with newly diagnosed GCTs, as well as cisplatin-sensitive GCT cell line xenografts and their resistant variants for all histological variants of GCTs. GSTM1 expression was detected by reverse transcription-quantitative PCR and immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method. GSTM1 expression was correlated with patient/tumor characteristics and treatment outcomes. The highest GSTM1 expression was observed in seminoma, followed by choriocarcinoma, embryonal carcinoma, and yolk sac tumor, while the lowest was observed in teratoma (p<0.0001). There was no association between GSTM1 expression in tumor tissue and patient/tumor characteristics. The low GSTM1 expression was associated with significantly better relapse-free survival compared with high GSTM1 (HR=0.50, 95% CI 0.23-1.09, p=0.03) but not overall survival (HR=0.61, 95% CI 0.24-1.54, p=0.22). Multivariate analysis showed that the prognostic value of GSTM1 was independent of the International Germ Cell Cancer Collaborative Group (IGCCCG) score. These data revealed the prognostic value of GSTM1 in GCTs, with a high GSTM1 expression associated with worse outcomes, suggesting that GSTM1 could be responsible, in part, for treatment resistance in GCTs.

A Case of Non-Seminomatous Germ Cell Tumor Complicated by Tumor Thrombus in an Active Duty Soldier.

Testicular malignancies commonly affect adolescent and young adult males. Although they tend to respond well to cisplatin-based chemotherapy with excellent overall survival, complications such as inferior vena cava tumor thrombus are rare and can be associated with high morbidity and mortality. We present a case of tumor thrombus in a 21-year-old active duty male with a newly diagnosed stage IIIB non-seminomatous germ cell tumor presenting with extensive left lower extremity swelling. Ultrasound with Doppler was notable for significant thrombus of the left common femoral, femoral, and popliteal vein. Computed tomography imaging revealed extensive thrombus of the inferior vena cava, left iliac veins, and left gonadal vein with sparing of the left renal vein. Endovascular thrombectomy was performed with pathologic analysis confirming the presence of malignant cells consistent with tumor thrombus. The patient continued subsequent non-seminomatous germ cell tumor treatment without complications.

Current outstanding challenges in germ cell tumors.

Despite the remarkable advances in the treatment of germ cell tumors (GCT), several challenges remain. This review aims to highlight some of these challenges and provide guidance on how to navigate through them. Patients with International Germ Cell Cancer Collaborative Group poor risk disease have worse prognosis and investigating novel therapeutic interventions are warranted in this population. Patients with brain metastases require a multidisciplinary approach by a group of clinicians experienced in the management of germ cell tumors. Patients with platinum refractory disease have poor prognosis and development of novel treatment options is urgently needed. Conventional tumor markers including alpha fetoprotein and human chorionic gonadotropin remain standard. Development of novel biomarkers to detect minimal residual disease or teratoma is needed. Management of patients with GCT requires a multidisciplinary approach. Patients should preferably be evaluated at tertiary care centers with expertise in the management of this disease.

Growing teratoma syndrome in an adolescent with a testicular germ cell tumor: a case report

Growing teratoma syndrome (GTS) is a condition characterized by a paradoxical increase in tumor size during or after chemotherapy and/or surgical treatment for germ cell tumors. Due to its relative rarity, GTS may be misinterpreted as disease progression. However, a decrease in tumor markers (alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG)) in the blood, a paradoxical increase in tumor size during chemotherapy, and a verified histological diagnosis of mature teratoma after the tumor removal confirm GTS. Here we report a clinical case of a patient in whom we observed a decrease in tumor markers (AFP and hCG) in the blood during treatment, a paradoxical increase in the tumor size and normal AFP and hCG levels 5 months after the end of chemotherapy and a histologically verified diagnosis. These clinical features are consistent with the diagnostic criteria of GTS. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

Testicular GERM cell tumors treatment outcome in a national cancer institution in Peru.

e17031 Background: Testicular germ cell tumor (TGCT) is the most common neoplasm in young men and the incidence has been increasing over the last few decades, especially among Hispanic men. Multidisciplinary management is associated with excellent oncological outcomes. Here, we describe the treatment outcome of TGCT patients treated in single institution in Peru. Methods: We conducted a retrospective study of TGCT treated at Instituto Nacional de Enfermedades Neoplasicas from 2016 to 2019. Clinical and pathological data were collected from medical records. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and compared with long-rank test. A level of p &lt; 0.05 was considered significant. The statistical package SPSS v19 was used for the data analysis. Results: 221 patients were identified, 56% were non-seminomatous (NS) and 44% were seminomatous (S). Orchiectomy was performed in 94% of patients, only 6% underwent orchiectomy after chemotherapy. In both groups, the treatment regimens were: BEP (Bleomycin/Etoposide/cisplatin) 90%, Carboplatin 8.1% and EP (Etoposide/Cisplatin) 1.8%. 42 (21%) of patients receive rescue therapy, being the most frequent TIP (paclitaxel/ifosfamide/cisplatin). In NS patients, 5-year PFS was superior in good risk compared with poor risk (100% vs. 86%, p = 0.028) and for tumor markers level, S0 was superior to S3 (100% vs. 82%, p = 0.008). In S, 5-year PFS was no significant in any of groups of analysis. With a median follow-up of 57 months, OS in NS was 91%, 83% and 81% in 12, 36 and 60 months, respectively and OS in S was 96%, 87% and 87% in 12, 36 and 60 months, respectively. The analysis of 5-year OS according to clinical stage and risk stratification are shown in the Table 1. Only 2 patients received high-dose chemotherapy and still in complete response. Conclusions: Despite the high incidence of advanced TGCT, our patients had excellent survival results; being lower in those with CS III (both NS and S groups), poor risk and S3 for NS, and intermediate risk for S. Multidisciplinary management in a high volume institution is important for better outcomes in our patients. [Table: see text]

Balancing efficacy with long-term side-effects: can we safely de-escalate therapy for germ cell tumors?

ABSTRACT Introduction The success in the management of germ cell tumors has encouraged researchers to pay more attention on long-term side effects and other survivorship issues. The de-escalation of treatment is intended to reduce side effects but must be balanced against any compromise of efficacy. Cisplatin-based therapy is the cornerstone of treatment for germ cell tumors. However, they can result in acute and long-term side effects, including ototoxicity, neurotoxicity, nephrotoxicity, and increased risk of second malignancies. Areas covered This review discusses approaches of de-escalation including biomarker-directed treatment using microRNAs, surveillance for immature teratoma, the use of carboplatin monotherapy for seminoma, and the option of non-cisplatin-based approaches in relapsed germ cell tumors. Expert opinion While the results with the current standard options in terms of cancer control are very good, the price being paid in terms of long-term side effects is considerable.

Immature Teratoma with Growing Teratoma Syndrome and Gliomatosis Peritonei Coexistence.

Ovarian germ cell tumours constitute 5% of all ovarian cancers. During the natural course and treatment of these tumours , there may be more unusual cases. One of them is gliomatosis peritonei, which is characterised by the spread of glial cells on the peritoneal surfaces, while the other one is growing teratoma syndrome characterised by the rapid growth of benign component and loss or shrinkage of the malignant component in response to systemic chemotherapy during the treatment of germ cell tumours. Herein, we present a case of coexistence of gliomatosis peritonei and growing teratoma syndrome during the treatment of a 29-year female with immature ovarian teratoma. Key Words: Germ cell tumours , Growing teratoma syndrome, Gliomatosis peritonei, Ovaries.

PD-L1 and PD-1 expression in pediatric central nervous system germ cell tumors

Central nervous system (CNS) germ cell tumors (GCTs) represent 2–3% of all primary CNS tumors. The majority are germinomas, which are radiosensitive and have an excellent prognosis. Contrarily, CNS non-germinomatous GCTs (NGGCTs) have less favorable prognosis and require more aggressive treatment. The expression of checkpoint/immune markers in CNS GCTs, particularly NGGCTs, is unknown. We previously reported a case of a patient whose intracranial NGGCT (predominantly choriocarcinoma) responded to immune checkpoint inhibition therapy. This case led us to evaluate our archive of intracranial GCTs for expression of PD-L1 and PD-1. With IRB approval, we searched the pathology archives at our institution for CNS GCTs. Demographic, radiologic, clinical, and histologic information was extracted from the medical records. Immunohistochemistry for lymphocytic markers (CD4, CD8, CD20), PD-1, and PD-L1 was performed. PD-L1 was considered positive if greater than 1% of tumor cells were positive and PD-1 was reported as a percentage of positive inflammatory cells. Fifty cases were identified, including 28 germinomas (mean age at diagnosis: 15.5 years; 17 males, 11 females), and 22 NGGCTs (mean age at diagnosis: 12.0 years, 21 males, 1 female). Germinomas were mostly suprasellar (17/28) and NGGCTs were predominantly pineal (17/22). Twenty-two germinomas (79%) were positive for PD-L1 expression, and 13 NGGCTs (57%) were positive for PD-L1. Cases of choriocarcinoma showed the most diffuse PD-L1 expression. PD-1 expression was seen in lymphocytes among 27/28 of the germinomas and 20/23 of the NGGCTs (ranging from 1–40% of lymphocytes). As expected, larger quantities of inflammatory cells were present in cases of germinoma. We demonstrate immune activity in CNS GCTs, and our results suggest that immune checkpoint inhibitors may be efficacious in the treatment of intracranial GCTs. Among NGGCTs, cases of choriocarcinoma showed the highest expression of PD-L1 in tumor cells, suggesting that this subtype may have the greatest benefit from checkpoint blockade.

Paclitaxel, ifosfamide, cisplatin (TIP) for the treatment of intermediateand poor-risk nonseminomatous germ cell tumors with an inadequate decrease in tumor markers: a phase II study

Purpose: To evaluate efficacy of TIP (paclitaxel, ifosfamid, cisplatin) in the 1st line treatment of germ cell tumors patients with unfavorable decline of serum tumor markers after 1 cycle of the standard regimen of chemotherapy. Patients and methods: In this phase II multicenter, nonrandomized trial, patients were enrolled from 4 centers of the Russian Federation. Patients were included if they were older than 18 years, had evidence of testicular, retroperitoneal, or mediastinal nonseminoma based on histologic findings or clinical evidence (high serum human chorionic gonadotropin or alpha-fetoprotein levels) that matched International Germ Cell Cancer Consensus Group (IGCCCG) intermediate and poor prognosis criteria. All patients got one cycle of BEP regimen (bleomycin 30 mg on days 1, 3, 5, etoposide 100 mg / m 2 on days 1–5, cisplatin 20 mg / m 2 on days 1–5). Patients with unfavorable serum tumor markers decline after the first cycle of chemotherapy at day 18–21 received four cycles of TIP regimen (paclitaxel 120 mg / m 2 on days 1–2, ifosfamide 1500 mg / m 2 on days 2–5, and cisplatin 25 mg / m 2 om days 2–5, granulocyte-colony stimulating factor 5 mg / kg on days 6–15). In the presence of a residual tumor larger than 1 cm and the technical possibility of its removal, surgical treatment was performed. The primary endpoint was 1-year progression-free survival. Results: Between 2017 and 2021, 28 patients were included in our study: seven patients with an intermediate prognosis according to IGCCCG classification and twenty-one with poor risk. Median follow-up was 15,5 months (range, 4,4–38,3 months). The 1-year progression-free survival and overall survival in intention-to-treat population were 76,6 % and 81,0 %, respectively. One-year progression-free survival and overall survival according IGCCCG classification were 100 % and 100 % for an intermediate risk patients and 68 % and 73,8 % for a poor risk, respectively. The favorable response rate (complete response + partial response with normalization STM) was observed in 19 (68 %) patients. During the follow-up period, disease progression was noted in 9 (32 %) patients, 7 (25 %) patients died, including one from an aggressive growing mature teratoma syndrome. Eleven (39 %) patients underwent surgical treatment: retroperitoneal lymph node dissection (55 %), mediastinal lymph node dissection (36 %), pulmonary resection (9 %). Pathological complete response was achieved in 6 (55 %) patients, mature teratoma — 2 (18 %), viable tumour — 3 (27 %). TIP showed acceptable safety profile and only in one case tumor lysis syndrome was observed. Conclusions: The TIP regimen may improve the results of treatment in the first line with unfavorable decrease of serum tumor markers after the first cycle of chemotherapy, which requires further study in a randomized trial.

How to classify, diagnose, treat and follow-up extragonadal germ cell tumors? A systematic review of available evidence

PurposeTo present the current evidence and the development of studies in recent years on the management of extragonadal germ cell tumors (EGCT).MethodsA systematic literature search was conducted in Medline and the Cochrane Library. Studies within the search period (January 2010 to February 2021) that addressed the classification, diagnosis, prognosis, treatment, and follow-up of extragonadal tumors were included. Risk of bias was assessed and relevant data were extracted in evidence tables.ResultsThe systematic search identified nine studies. Germ cell tumors (GCT) arise predominantly from within the testis, but about 5% of the tumors are primarily located extragonadal. EGCT are localized primarily mediastinal or retroperitoneal in the midline of the body. EGCT patients are classified according to the IGCCCG classification. Consecutively, all mediastinal non-seminomatous EGCT patients belong to the “poor prognosis” group. In contrast mediastinal seminoma and both retroperitoneal seminoma and non-seminoma patients seem to have a similar prognosis as patients with gonadal GCTs and metastasis at theses respective sites. The standard chemotherapy regimen for patients with a EGCT consists of 3–4 cycles (good vs intermediate prognosis) of bleomycin, etoposid, cisplatin (BEP); however, due to their very poor prognosis patients with non-seminomatous mediastinal GCT should receive a dose-intensified or high-dose chemotherapy approach upfront on an individual basis and should thus be referred to expert centers Ifosfamide may be exchanged for bleomycin in cases of additional pulmonary metastasis due to subsequently planned resections. In general patients with non-seminomatous EGCT, residual tumor resection (RTR) should be performed after chemotherapy.ConclusionIn general, non-seminomatous EGCT have a poorer prognosis compared to testicular GCT, while seminomatous EGGCT seem to have a similar prognosis to patients with metastatic testicular seminoma. The current insights on EGCT are limited, since all data are mainly based on case series and studies with small patient numbers and non-comparative studies. In general, systemic treatment should be performed like in testicular metastatic GCTs but upfront dose intensification of chemotherapy should be considered for mediastinal non-seminoma patients. Thus, EGCT should be referred to interdisciplinary centers with utmost experience in the treatment of germ cell tumors.

Cisplatin Induced Ischemic Stroke in Germ cell tumour

Germ cell tumors are common among young males with excellent outcomes even in advanced stages. Despite a superb curability rate, treatment-related side effects and complications affect the quality of life. We report a case where Cisplatin-based chemotherapy, the backbone for germ cell tumors treatment, led to ischemic insult. The purpose is to highlight the importance of keeping the incidence of ischemic events following cisplatin-based chemotherapy in differentials for effective management.

Validation of testicular germ cell tumor staging in nationwide cancer registries.

Nationwide cancer registries such as the National Cancer Database and Surveillance, Epidemiology, and End Results rely on accurate data from tumor registries to formulate hypotheses and report outcomes and treatment patterns. We evaluated the accuracy of our institutional registry for testicular germ cell tumors by comparing data abstracted by urologists with data abstracted by registry. We performed a retrospective review of patients receiving initial diagnosis and treatment for germ cell tumors at our hospital system from 2005 to 2016. We compared coding for American Joint Committee on Cancer TNMS staging, overall composite stage, and first-line treatment between urologists and tumor registry at the time of diagnosis. Paired staging from registry and urologist was available for 80 patients. T, N, M, and S-staging were accurate for 90%, 81%, 94%, and 54% of records, respectively. Composite staging and first-line treatment were concordant for 39% and 90% of patients, respectively. A separate review of 33 Stage IS patients per registry for composite staging revealed 15% concordance. Our institutional tumor registry had substantial inconsistencies in accurately staging N stage, S stage, and thus, composite stage for testicular cancer. An educational intervention to improve abstraction by registry led to increased concordance. Assuming similar discrepancies may exist at other institutions and for other cancer types, caution should be used when interpreting staging data in nationwide cancer registries. This sheds light on the need for improved clarification of staging guidelines, dynamic institutional internal auditing, and training reform within cancer registries.

\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.

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.

Late relapsing germ cell tumors with elevated tumor markers

PurposeLate relapsing germ cell tumors (LR-GCT) are considered a rare distinct biologic entity as their clinical presentation and response to treatment is different to early recurrences. While serum tumor markers (AFP and ß-HCG) play an important role at the time of first diagnosis to correctly classify prognosis and treatment of germ cell tumors, they may not have the same significance in a late relapse situation.Patients and methodsThirty-seven patients with LR-GCT with elevated serum tumor markers were identified in our database. Twenty-six patients underwent primary surgical resection of the late relapsing tumor. Eleven patients received salvage chemotherapy and a post-chemotherapy residual tumor resection. Serum tumor markers, histological findings and oncological outcome were analyzed.ResultsIn the histopathological specimen, viable cancer was found in 20 cases (54%) and teratoma was found in 16 cases (43%). In nine cases (24%), a somatic-type malignant transformation was present. In 19 of 37 patients (51.4%), the late relapse specimen presented a histological type of GCT, which was not present in the primary histology. Twenty-two patients (59.5%) were included in follow-up analysis. Mean and median follow-up time was 62.2 and 53 months, respectively. Seventeen patients (77.3%) suffered a relapse or had progressive disease after LR therapy. Five patients (22.7%) have been relapse-free after LR therapy (mean FU 61.6 months). Ten patients died of disease during follow-up (45.5%) and had a mean time from LR to death of 66.4 months. Eleven patients were alive at last follow-up (mean FU 62.2 months). Relapse and survival rate were similar between patients who received primary resection of LR tumor and patients who received salvage chemotherapy followed by surgery.ConclusionPatients with a late relapsing germ cell tumor and elevated markers have a poor prognosis and a high risk for another relapse independent on primary treatment. The histological type and aggressiveness of a late relapsing tumor cannot be predicted with serum tumor marker levels at the time of diagnosis of LR. In up to 54% of cases, primary histology did not coincide with LR histology. Therefore, we propose primary surgical resection of a late relapsing tumor if a complete resection is feasible in order to gain exact histology and tailor further treatment.

Current Management of Refractory Germ Cell Tumors.

Germ cell tumors (GCTs) are the most common solid tumors affecting men between ages of 20 and 34 years. Most of the cases, even in advanced disease, will have good prognosis. However, around 20-30% of advanced disease will be refractory or develop relapse after treatment. Herein, we review the current management of refractory/relapsed GCTs. Salvage treatment of GCTs has been a controversial topic for the last few decades. Conventional dose chemotherapy (CDCT), high-dose chemotherapy (HDCT) with stem cell infusion, and surgical salvage were proven to be effective and curative options in some cases. The international randomized trial (TIGER) will ultimately answer which chemotherapy approach may be optimal. Furthermore, the usage of immunotherapy is still under investigation with limited data so far in the setting of relapsed/refractory GCTs. Curative paradigms including with CDCT and HDCT are possible, although novel approaches beyond HDCT are still needed to eliminate mortality from this disease.

Abstract 632: Growth hormone deficiency in childhood germ cell tumor survivors

Abstract Introduction: Germ cell tumors (GCTs) are a rare heterogenous group of cancers accounting for 3% of childhood cancers and 15% of cancers in adolescents. Cure rates for GCTs exceed 90% and GCTs currently comprise the 3rd largest group of childhood cancer survivors in the United States. Little systematic evidence exists on late effects of cancer treatment in this group. Treatment for GCTs includes some combination of chemotherapy, radiation, and gonadectomy; interventions that place survivors at high risk for developing endocrinopathies. One of the most common endocrinopathies experienced by childhood cancer survivors is growth hormone deficiency (GHD). In this analysis, we evaluated the prevalence of growth hormone deficiency among GCT survivors. Methods: Participants were previously enrolled in the Germ Cell Tumor Epidemiology Study (GaMETES), which is a case parent triad study conducted using the Children's Oncology Group registry protocols. Data on late effects and outcomes are currently available for a subset of the participants who have provided additional consent for a follow-up study including a self-administered questionnaire and medical record retrieval. GHD was identified via self-report and validated through medical records. Treatment information was abstracted from the medical records. Results: In this interim analysis, 230 participants completed the self-administered questionnaire, including 61 with ovarian tumors, 40 with testicular tumors, 38 extragonadal tumors, and 92 intracranial tumors. Thirty-six of the participants reported having growth hormone deficiency (GHD), all of whom had intracranial germ cell tumors (iGCTs). Thus, the prevalence of GHD among iGCT survivors was 39.1%. We validated 45 questionnaire responses against chart review of iGCT patients. Among these 45, 24 (53.33%) iGCT survivors had GHD. Participants who were treated with high doses of cranial radiation (&amp;gt;30 Gy) were more likely to have GHD (OR = 2.3, 95% CI 0.4-13.1). Conclusions: Growth hormone deficiency is highly prevalent in survivors of childhood intracranial germ cell tumors. The increased prevalence is likely related to the propensity for germ cell tumor involvement of the pituitary stalk, chemotherapy and cranial radiation. Exposure to higher cumulative doses of cranial radiation is associated with higher risk for developing growth hormone deficiency. Citation Format: Diana W. Lone, Karim T. Sadak, Bradley S. Miller, Aubrey K. Hubbard, Jeannette Sample, Michelle Roesler, Jenny N. Poynter. Growth hormone deficiency in childhood germ cell tumor survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 632.

Serum tumour markers in germ cell tumours: From diagnosis to cure.

Germ cell tumors (GCTs) represent the best and the only example of solid tumors curable in the large majority of patients. GCTs are one of the few malignancies for which specific biochemical markers have been identified: human chorionic gonadotropin (HCG) and alfa-fetoprotein (AFP). Due to their specificity and sensitivity they constitute formidable tools in the diagnosis and monitoring of treatment for GCTs. As a tumor mass marker, lactate dehydrogenase (LDH) is also considered. Tumor markers are expressed in 15-20% of seminoma and 60-80% of non-seminoma. With the aim to increase sensitivity and specificity, recent studies have proposed miRNAs as serum biomarkers. This review will focus on role of serum tumor markers in diagnosis, staging, prognosis, monitoring of response, and finally follow-up of GCTs.

First person profile: George J. Bosl, MD: Former long-term chair of Memorial Sloan Kettering Cancer Center's Department of Medicine reflects on his multifaceted career.

First person profile: George J. Bosl, MD: Former long-term chair of Memorial Sloan Kettering Cancer Center's Department of Medicine reflects on his multifaceted career.