The Effect of Socioeconomic Status and Race/Ethnicity on the Risk of Presenting With Advanced Stage at Diagnosis in Embryonal Tumors.

We evaluated whether socioeconomic status (SES), race/ethnicity, and their interaction were associated with the presentation of advanced stage at diagnosis in embryonal tumors. Children 0 to 19 years of age diagnosed with embryonal tumors between 2006 and 2018 were identified from the US Surveillance, Epidemiology, and End Results program database specialized with Census Tract SES/Rurality. SES quintile was derived from a composite index for census tracts. We performed logistic regression to estimate odds ratios (ORs) and 95% confidence intervals by SES and race/ethnicity, adjusting for sex, age, and diagnosis year. Overall, no significant associations were found between either SES or race/ethnicity and the risk of presenting with advanced stage at diagnosis, although patterns of risk reductions were observed in atypical teratoid/rhabdoid tumors and embryonal rhabdomyosarcoma with increasing SES. In the stratified analysis, decreased odds of presenting with advanced-stage embryonal rhabdomyosarcoma were observed for Hispanics with higher SES (OR: 0.24, 95% Confidence Interval: 0.08-0.75) compared with Hispanics with lower SES. Future studies incorporating individual-level SES, cancer-specific staging information, and potential demographic, clinical, epidemiological, and genetic risk factors are warranted to confirm our findings.

Occupational exposure to organic solvents and the risk of developing testicular germ cell tumors (TESTIS study): Effect of combined exposure assessment on risk estimation.

OBJECTIVES: Etiological factors of testicular germ cell tumors (TGCT) remain largely unknown, but a causal role of occupational exposures to solvents has been suggested. Previous studies analyzing these exposures reported discordant results, potentially related to exposure assessment methods. The aim of this study was to investigate the role of occupational exposure to solvents on the risk of developing TGCT among young men. METHODS: This study examined occupational exposures to solvents and TGCT risk based on the lifetime work histories of 454 cases and 670 controls, aged 18-45 years, of the French national TESTIS case-control study. Solvent exposure was estimated using: (i) exposure assignment by job-exposure matrix (JEM) and (ii) JEM combined with self-reported exposure data from specific questionnaires (SQ) and expert assessment (EA). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. RESULTS: Both approaches (JEM and JEM+SQ+EA) showed a consistent association between TGCT and trichloroethylene exposure (exposed versus not exposed; JEM=OR 1.80 [95% confidence interval (CI) 1.12-2.90] and JEM+SQ+EA= OR 2.59 (95% CI 1.42-4.72). Both approaches also observed positive associations with ketone esters and fuels & petroleum-based solvents. CONCLUSION: The results suggest that some organic solvents might be involved in the pathogenesis of TGCT among occupationally exposed men. The combined use of JEM+SQ+EA seemed to limit misclassification by considering individual exposure variability and is, therefore, an appealing approach to assess occupational exposures in epidemiological studies.

Large Malignant Testicular/Paratesticular Tumors in Adolescence: Assessment of Gross Tumor Size in a Vulnerable Age Group.

OBJECTIVE: We hypothesized that reticence to address a groin mass may result in late presentation of testicular/paratesticular malignancy in early puberty through adolescence. METHODS: Malignant testicular and paratesticular tumors (malignant germ cell tumors and rhabdomyosarcomas) diagnosed at our institution from 1994-2023 for patients aged 11-20 were included. Clinicopathologic features were recorded, and statistically analyzed. RESULTS: Eighty-five cases were identified. Patient ages ranged from 11 to 20 years (mean 17 years, median 16 years). The greatest tumor dimension ranged from 0.8 to 18.0 cm (mean 4.4 cm, median 3.5 cm). Ten tumors (11.8% of cases) were ≥10.0 cm. In the 11-13-year-old age group, 100% of tumors (3/3) were ≥10 cm. The proportion of tumors ≥10 cm was significantly higher in the 11-13-year-old age group than in either the 14-16-year-old (P<0.001) or 17-20-year-old (P<0.001) age groups. CONCLUSION: This adolescent cohort with malignant testicular and paratesticular tumors showed a high proportion (11.8%) of very large (≥10 cm) tumors. Although the reasons are unknown and likely multifactorial, this study suggests that adolescents, particularly the 11-13 year age group, are a vulnerable population.

Assessment of the impact of direct in vitro PFAS treatment on mouse spermatozoa.

Abstract: Poly- and per-fluoroalkyl substances (PFAS) are synthetic environmentally persistent chemicals. Despite the phaseout of specific PFAS, their inherent stability has resulted in ubiquitous and enduring environmental contamination. PFAS bioaccumulation has been reported globally with omnipresence in most populations wherein they have been associated with a range of negative health effects, including strong associations with increased instances of testicular cancer and reductions in overall semen quality. To elucidate the biological basis of such effects, we employed an acute in vitro exposure model in which the spermatozoa of adult male mice were exposed to a cocktail of PFAS chemicals at environmentally relevant concentrations. We hypothesized that direct PFAS treatment of spermatozoa would induce reactive oxygen species generation and compromise the functional profile and DNA integrity of exposed cells. Despite this, post-exposure functional testing revealed that short-term PFAS exposure (3 h) did not elicit a cytotoxic effect, nor did it overtly influence the functional profile, capacitation rate, or the in vitro fertilization ability of spermatozoa. PFAS treatment of spermatozoa did, however, result in a significant delay in the developmental progression of the day 4 pre-implantation embryos produced in vitro. This developmental delay could not be attributed to a loss of sperm DNA integrity, DNA damage, or elevated levels of intracellular reactive oxygen species. When considered together, the results presented here raise the intriguing prospect that spermatozoa exposed to a short-term PFAS exposure period potentially harbor an alternate stress signal that is delivered to the embryo upon fertilization. Lay summary: PFAS are synthetic chemicals widely used in non-stick cookware, food packaging, and firefighting foam. Such extensive use has led to concerning levels of environmental contamination and reports of associations with a spectrum of negative health outcomes, including testicular cancer and reduced semen quality. To investigate the effects of PFAS on male reproduction, we incubated mouse sperm in a cocktail of nine PFAS at environmentally relevant concentrations before checking for a range of functional outcomes. This treatment strategy was not toxic to the sperm; it did not kill them or reduce their motility, nor did it affect their fertilization capacity. However, we did observe developmental delays among pre-implantation embryos created using PFAS-treated sperm. Such findings raise the intriguing prospect that PFAS-exposed sperm harbor a form of stress signal that they deliver to the embryo upon fertilization.

Delivered relative dose intensity in adolescent and young adult germ cell tumours in England: Assessment of data quality and consistency from clinical trials compared to national cancer registration data.

Adolescent and young adults (AYA) with germ cell tumours (GCT) have poorer survival rates than children and many older adults with the same cancers. There are several likely contributing factors to this, including the treatment received. The prognostic benefit of intended dose intensity is well documented in GCT from trials comparing regimens. However, evidence specific to AYA is limited by poor recruitment of AYA to trials and dose delivery outside trials not being well examined. We examined the utility of cancer registration data and a clinical trials dataset to investigate the delivery of relative dose intensity (RDI) in routine National Health Service practice in England, compared to within international clinical trials. Linked data from the Cancer Outcomes and Services Dataset (COSD) and the Systemic Anti-Cancer Therapy (SACT) dataset, and data from four international clinical trials were analysed. Survival over time was described using Kaplan-Meier estimation; overall, by age category, International Germ-Cell Cancer Collaborative Group (IGCCCG) classification, stage, tumour subtype, primary site, ethnicity and deprivation. Cox regression models were used to determine the fully adjusted effect of RDI on mortality risk. The quality of both datasets was critically evaluated and clinically enhanced. RDI was found to be well maintained in all datasets with higher RDIs associated with improved survival outcomes. Real-world data demonstrated several strengths, including population coverage and inclusion of sociodemographic variables and comorbidity. It is limited in GCT however, by the poor completion of data items enabling risk classification of patients and a higher proportion of missing data.

Epidemiology, Management, and Survival Outcomes of Germ Cell Cancer in Southern Portugal: A Population-Based Study (2008-2012).

INTRODUCTION: Building on previous suboptimal survival results, we aimed to perform a study of the epidemiological status, management, and outcomes of germ cell tumors (GCT) in the Portuguese population. MATERIALS AND METHODS: Retrospective populational study of GCT cases diagnosed between 2008 and 2012 in southern Portugal. Joinpoint regression was used to compute average annual percentage change (AAPC) in incidence rate. ESMO/EAU guidelines served as references to evaluate compliance. Association between compliance with guidelines and hospital GCT case load was performed by generalized estimating equation. Survival was calculated by Kaplan-Meier and prognostic factors by Cox models. RESULTS: The study included 401 GCT male cases. The AAPC was 5.4% (IC 95% 3.3-7.4, P < .001) from 1999 (an earlier cohort published) to 2012. The median time to diagnosis was 63 days (Q25 = 33 days; Q75 = 114 days; IQR = 81 days). For stage II/III the median time to start chemotherapy was 34 days (Q25 = 22 days; Q75 = 56 days; IQR = 22 days). In 86% cases there was noncompliance with guidelines for the orchiectomy report, 6% for staging, 38% for tumor markers evaluation, 20% for treatment and 25% for chemotherapy dose intensity. The 5-year overall survival was 93.8% (95% CI, 91.3%-96.4%). Hospitals that managed ≤ 3 GCT cases/ year had higher odds for noncompliance with guidelines of blood markers, treatment and dose intensity. None of GCT healthcare access and management factors studied were associated with prognosis. CONCLUSIONS: The burden of GCT is rising in Portugal. Although survival has improved, efforts must be made to nationally enhance training and expertise in GCT and support region adapted models of centralization of care.

Differences in future life expectancy of testicular germ-cell tumor patients vs. age-matched male population-based controls.

BACKGROUND: It is unknown whether five-year overall survival (OS) differs and to what extent between testicular germ-cell tumor (TGCT) patients and age-matched male population-based controls. MATERIALS: We identified newly diagnosed (2004-2014) TGCT patients within Surveillance Epidemiology and End Results database 2004-2019. We compared OS between non-seminoma (NS-TGCT) and seminoma (S-TGCT) patients relative to age-matched male population-based controls based on Social Security Administration Life-Tables. Smoothed cumulative incidence plots displayed cancer-specific mortality (CSM) vs. other-cause mortality (OCM). RESULTS: Of all 20,935 TGCT patients, 43% had NS-TGCT and 57% had S-TGCT. Of NS-TGCT patients, 63% were stage I vs. 16% stage II vs. 21% stage III. Of S-TGCT patients, 86% were stage I vs. 8% were stage II vs. 6% stage III. Five-year OS differences between NS-TGCT patients vs age-matched male population-based controls were 97 vs. 99% (Δ = 2%) for stage I, 96 vs. 99% (Δ = 3%) for stage II, 76 vs 98% (Δ = 22%) for stage III. Five-year OS differences between S-TGCT patients vs age-matched male population-based controls were 97 vs. 98% (Δ = 1%) for stage I, 95 vs. 97% (Δ = 2%) for stage II, 87 vs. 98% (Δ = 11%) for stage III. OCM rates ranged from 1 to 3% in NS-TGCT patients and from 2 to 4% in S-TGCT patients. CONCLUSION: The OS difference between NS-TGCT patients vs. age-matched male population-based controls was invariably higher across all stages (2-22%) than for S-TGCT patients (1-11%). Reassuringly, OCM rates were marginal in stage I and stage II patients. Conversely, higher OCM rates were recorded in stage III patients.

German specialists treating testicular cancer follow different guidelines with resulting inconsistency in assessment of retroperitoneal lymph-node metastasis: clinical implications and possible corrective measures.

BACKGROUND: Testicular germ cell tumors (GCTs) are aggressive but highly curable tumors. To avoid over/undertreatment, reliable clinical staging of retroperitoneal lymph-node metastasis is necessary. Current clinical guidelines, in their different versions, lack specific recommendations on how to measure lymph-node metastasis. OBJECTIVE: We aimed to assess the practice patterns of German institutions frequently treating testicular cancer for measuring retroperitoneal lymph-node size. METHODS: An 8-item survey was distributed among German university hospitals and members of the German Testicular Cancer Study Group. RESULTS: In the group of urologists, 54.7% assessed retroperitoneal lymph nodes depending on their short-axis diameter (SAD) (33.3% in any plane, 21.4% in the axial plane), while 45.3% used long-axis diameter (LAD) for the assessment (42.9% in any plane, 2.4% in the axial plane). Moreover, the oncologists mainly assessed lymph-node size based on the SAD (71.4%). Specifically, 42.9% of oncologists assessed the SAD in any plane, while 28.5% measured this dimension in the axial plane. Only 28.6% of oncologists considered the LAD (14.3% in any plane, 14.3% in the axial plane). None of the oncologists and 11.9% of the urologists (n = 5) always performed an MRI for the initial assessment, while for follow-up imaging, the use increased to 36.5% of oncologists and 31% of urologists. Furthermore, only 17% of the urologists, and no oncologists, calculated lymph-node volume in their assessment (p = 0.224). CONCLUSION: Clear and consistent measurement instructions are urgently needed to be present in all guidelines across different specialistic fields involved in testicular cancer management.

Fertility and prognosis assessment between bleomycin/etoposide/cisplatin and paclitaxel/carboplatin chemotherapy regimens in the conservative treatment of malignant ovarian germ cell tumors: a multicenter and retrospective study.

OBJECTIVE: To evaluate the impact of bleomycin/etoposide/cisplatin (BEP) and paclitaxel/carboplatin (PC) chemotherapy regimens on the fertility and prognostic outcomes in malignant ovarian germ cell tumor (MOGCT) patients who underwent fertility-sparing surgery (FSS). METHODS: A propensity score matching algorithm was performed between the BEP and PC groups. The χ² test and the Kaplan-Meier method were used to compare the fertility outcome, disease-free survival (DFS) and overall survival (OS). The Cox proportional hazards regression analysis was used to identify risk factor of DFS. RESULTS: We included 213 patients, 185 (86.9%) underwent BEP chemotherapy, and 28 (13.1%) underwent PC chemotherapy. The median age was 22 years (range, 8-44 years), and the median follow-up period was 63 months (range, 2-191 months). Fifty-one (29.3%) patients had a pregnancy plan, and 35 (85.4%) delivered successfully. In the before and after propensity score matching cohorts, there were no significant differences in spontaneous abortion, selective termination of pregnancy, during-pregnancy status, and live birth between the BEP and PC groups (p>0.05). Fourteen (6.6%) patients experienced recurrence, including 11 (5.9%) in the BEP group and 3 (10.7%) in the PC group. Four (1.9%) patients in the BEP group died. Kaplan-Meier analysis revealed no significant differences in DFS (p=0.328) and OS (p=0.446) between the BEP and PC groups, and the same survival results were observed in the after matching cohort. CONCLUSION: The PC regimen is as safe as the BEP regimen for MOGCT patients with fertility preservation treatment, and no differences were observed in fertility and clinical prognosis.

Parental occupations at birth and risk of adult testicular germ cell tumors in offspring: a French nationwide case-control study.

Background: Testicular germ cell tumors (TGCT) are the most frequent cancer in young men in developed countries. Parental occupational exposures during early-life periods are suspected to increase TGCT risk. The objective was to estimate the association between parental occupations at birth and adult TGCT. Methods: A case-control study was conducted, including 454 TGCT cases aged 18-45 from 20 French university hospitals, matched to 670 controls based on region and year of birth. Data collected from participants included parental jobs at birth coded according to the International Standard Classification of Occupation-1968 and the French nomenclature of activities-1999. Odds ratios (OR) for TGCT and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for TGCT risk factors. Results: Paternal jobs at birth as service workers (OR = 1.98, CI 1.18-3.30), protective service workers (OR = 2.40, CI 1.20-4.81), transport equipment operators (OR = 1.96, CI 1.14-3.37), specialized farmers (OR = 2.66, CI 1.03-6.90), and maternal jobs as secondary education teachers (OR = 2.27, CI 1.09-4.76) or in secondary education (OR = 2.35, CI 1.13-4.88) were significantly associated with adult TGCT. The risk of seminoma was increased for the above-mentioned paternal jobs and that of non-seminomas for public administration and defence; compulsory social security (OR = 1.99, CI 1.09-3.65); general, economic, and social administration (OR = 3.21, CI 1.23-8.39) for fathers; and secondary education teacher (OR = 4.67, CI 1.87-11.67) and secondary education (OR = 3.50, CI 1.36-9.01) for mothers. Conclusion: Some paternal jobs, such as service workers, transport equipment operators, or specialized farmers, and maternal jobs in secondary education seem to be associated with an increased risk of TGCT with specific features depending on the histological type. These data allow hypotheses to be put forward for further studies as to the involvement of occupational exposures in the risk of developing TGCT, such as exposure to pesticides, solvents, or heavy metals.

Assessment of prognostic and reproductive outcomes of omentectomy for patients with clinically apparent early-stage (I, II) malignant ovarian germ cell tumours: A multicentre retrospective study.

OBJECTIVE: This study assessed the effect of omentectomy on the prognosis and fertility in patients with clinically early-stage (I, II) malignant ovarian germ cell tumours (MOGCT). DESIGN: A retrospective multicentre study. SETTING: Four university teaching hospitals in China. POPULATION: A total of 268 patients with clinically apparent early-stage (I, II) MOGCT. METHODS: Data were obtained from the medical records. Additionally, the propensity score matching (PSM) algorithm was adopted. MAIN OUTCOME MEASURES: Prognostic outcomes were disease-free survival (DFS) and overall survival (OS). Fertility outcomes were pregnancy and live birth rates. RESULTS: A total of 187 (69.8%) patients underwent omentectomy. Kaplan-Meier analysis showed no significant differences in DFS and OS between the omentectomy and non-omentectomy groups before and after PSM (p > 0.05). Additionally, subgroup analysis stratified by age (<18 and ≥18 years) showed similar results. International Federation of Gynecology and Obstetrics (FIGO) stage was the only risk factor associated with DFS (hazard ratio [HR] 14.71, 95% confidence interval [CI] 4.47-48.38, p < 0.001) and OS (HR 37.36, 95% CI 3.87-361.16, p = 0.002). Pregnancy and live birth rates in the total population were 80.3% and 66.7%, respectively. There were no significant differences between the two groups before and after PSM. CONCLUSIONS: Omentectomy did not improve survival or affect fertility in patients with clinically apparent early-stage (I, II) MOGCT, regardless of the age. The clinical FIGO stage was an independent risk factor for recurrence and death.

Analysis of the Direct Cost of Medical and Surgical Care for Testicular Cancer in Early and Advanced Stages in a Third Level Medical Facility of the Mexican Social Security Institute.

BACKGROUND: The testicular cancer prevails in the third decade of life, the care cost increases with higher staging of the disease. OBJECTIVE: Compare the direct costs of medical and surgical attention for testicular cancer in early and advanced stages in a Third Level Medical Facility. MATERIAL AND METHODS: Process study, direct costs of medical attention are evaluated. Number of laboratory studies, imaging studies, and medical and surgical treatment were analyzed. The patients were divided into 2 groups: group 1 early stages and group 2 advanced stages. Mann Whitney U test was used for the difference between groups. RESULTS: There were 10 patients in each group, Group 1: 8 (80%) seminomas and 2 (20%) non-seminoma, Group 2: 4 (40%) seminomas and 6 (60%) non-seminomas. The average cost of care in Group 2 is higher than in Group 1, $288,827.90 and $145,911.70 Mexican pesos respectively (p=0.00578). CONCLUSIONS: The direct cost of medical attention is higher in the advanced stages compared to the early stages.

Molecular assessment of paratesticular rhabdomyomas demonstrates recurrent findings, including a novel H3C2 p.K37I mutation.

Rhabdomyomas are benign tumors with skeletal muscle differentiation that are broadly divided into cardiac and extracardiac types. The latter demonstrate a predilection for head and neck and genital locations and are further subclassified into adult-type rhabdomyoma (ATRM), fetal-type rhabdomyoma (FTRM) and genital rhabdomyoma (GRM). Most extracardiac rhabdomyomas that arise in paratesticular tissues have a somewhat distinctive morphology and have been termed sclerosing rhabdomyomas (SRM). Therefore, we hypothesized that these tumors may harbor recurrent genetic alterations. In this study, we assessed 15 paratesticular rhabdomyomas (11 initially classified as SRM, 2 cellular FTRM and 2 ATRM) using massively parallel DNA and RNA sequencing. Five of 14 successfully sequenced cases harbored a novel H3C2 p.K37I mutation (4 SRM and 1 ATRM). This mutation replaced a highly conserved lysine residue that is a target for epigenetic modifications and plays a role in regulation of DNA replication. Moreover, 4 tumors (2 cellular FTRM, 1 case initially diagnosed as SRM and 1 ATRM) had complex copy number profiles characterized by numerous chromosome-level and arm-level copy number gains, consistent with a ploidy shift. Rereview of the SRM with copy number gains demonstrated that it was significantly more cellular and had a more prominent fascicular architecture than the rest of the SRMs included in this series. Therefore, it was retrospectively reclassified as a cellular FTRM. In conclusion, this study demonstrated that paratesticular rhabdomyomas harbor recurrent somatic H3C2 p.K37I mutations and ploidy shifts.

Imaging response assessment for CNS germ cell tumours: consensus recommendations from the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group.

Homogeneous and common objective disease assessments and standardised response criteria are important for better international clinical trials for CNS germ cell tumours. Currently, European protocols differ from those of North America (the USA and Canada) in terms of criteria to assess radiological disease response. An international working group of the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group was therefore established to review existing literature and current practices, identify major challenges regarding imaging assessment, and develop consensus recommendations for imaging response assessment for patients with CNS germ cell tumours. New clinical imaging standards were defined for the most common sites of CNS germ cell tumour and for the definition of locoregional extension. These new standards will allow the evaluation of response to therapy in patients with CNS germ cell tumours to be more consistent, and facilitate direct comparison of treatment outcomes across international studies.

Predictive factors of diagnostic delay and effect on treatment patterns in testicular germ cell tumor patients.

BACKGROUND: Increased time from clinical symptom onset to diagnosis of testicular germ cell tumor (GCT), termed diagnostic delay (DD), is associated with an increased likelihood of metastatic disease at presentation. We assessed the association of patient factors on DD and subsequent treatment patterns. METHODS: The records for patients undergoing orchiectomy at a tertiary care hospital and safety net county hospital between 2006 and 2018 were obtained. Demographic variables, clinical symptoms, and post-diagnosis parameters were queried. Patient factors were assessed for association with DD by using both univariate and multivariable analyses. The effect of the Patient Protection and Affordable Care Act (PPACA) on DD was also studied. RESULTS: 201 patients received orchiectomy, and median DD was 38 days (IQR 14.5-122.5). Patients with metastatic disease had increased DD compared to those with localized disease (76 vs. 31 days, P < 0.001). Increased DD was associated with presentation to the safety net hospital (P = 0.001), non-white (P = 0.025), emergency department presentation (P = 0.025), uninsured (P = 0.01), testicular pain (P = 0.019), and presentation before 2014 (P = 0.047). DD was independently associated with presentation before 2014 (P = 0.004) on multivariate analysis. DD >38 days (i.e., above the median) was associated with increased receipt of adjuvant therapy (P = 0.001). CONCLUSION: PPACA implementation is associated with earlier detection of testicular cancer. Our findings highlight the impact of health care legislation on improving access of care to young men with cancer. Delay in diagnosis can lead to increased stage at presentation and need for adjuvant treatment. Further research to identify and overcome sociodemographic factors associated with diagnostic delay may lead to decreased treatment-related morbidity.

Multiparametric Framework Magnetic Resonance Imaging Assessment of Subtypes of Intracranial Germ Cell Tumors Using Susceptibility Weighted Imaging, Diffusion-Weighted Imaging, and Dynamic Susceptibility-Contrast Perfusion-Weighted Imaging Combined With Conventional Magnetic Resonance Imaging.

BACKGROUND: Intracranial germ cell tumors (iGCTs) are classified into two pathological subtypes (germinomas [GEs] and nongerminomatous germ cell tumors [NGGCTs]), with distinct treatment strategy and prognosis. Accurate preoperative determination of iGCT subtypes is essential to guide clinical decision-making and prognosis assessment. PURPOSE: To investigate the diagnostic value of diffusion-weighted imaging (DWI), susceptibility weighted imaging (SWI), and dynamic susceptibility-contrast perfusion-weighted imaging (DSC-PWI) combined with conventional magnetic resonance imaging (cMRI) in finding subtypes of iGCTs. STUDY TYPE: Retrospective. POPULATION: A total of 40 patients (45% male and 55% female) with iGCTs. FIELD STRENGTH/SEQUENCE: A 3 T; <T1WI, T2WI, T1WI + C, DWI, SWI, DSC-PWI>. ASSESSMENT: The parameters of DWI and DSC-PWI were calculated based on extracted parameters of multiparametric MRIs. The characteristics of SWI and cMRI were also compared in GEs and NGGCTs. STATISTICAL TESTS: The diagnostic efficacy of the minimum apparent diffusion coefficient (ADCmin), time-to-peak (TTP), relative mean transit time (rMTT), relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV) maps, and cMRI features in iGCT classification was evaluated by receiver operating characteristic curve (ROC) analyses. We calculated the sensitivity, specificity, AUC, and Youden index of the hybrid MR evaluation methods. A prospective cohort (five GEs and five NGGCTs) was designed as a simulation set to test the model. The significance threshold was set at P < 0.01. RESULTS: The ADCmin (1039.100 ± 453.830 vs. 1400.050 ± 394.650), rCBF values (20.650 ± 6.260 vs. 51.170 ± 6.570), and TTP values (24.450 ± 3.160 vs. 28.950 ± 5.120) were significantly lower in GEs than in NGGCTs. The combination of ADCmin, DSC-PWI, and cMRI showed the heights AUC (AUC = 0.962). The iGCT multiparametric framework showed the AUC was 0.958 in the simulation set. DATA CONCLUSION: The iCGT multiparametric framework might be an effective diagnostic approach of iGCT subtype. The application of cMRI (T1WI, T2WI, and Gd-T1WI) with advanced imaging modalities (DWI, SWI, and PWI) had the best performance for classifying iGCT subtypes. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Assessment of Resectability of Mediastinal Germ Cell Tumor Using Preoperative Computed Tomography.

BACKGROUND AND OBJECTIVES: Mediastinal germ cell tumor (MGCT) is a relatively rare tumor. Complete resection after chemotherapy is a standard treatment against this disease. However, the risk factors of incomplete resection are unclear. Therefore, we analyzed survival rates and risk factors for incomplete resection based on preoperative imaging. METHODS: We retrospectively reviewed the medical records of patients (n = 56) with MGCT operated at National Cancer Center Hospital, and analyzed preoperative computed tomography (CT) data in terms of relationship of the tumor and vessels, and investigated survival rate and risk factors for incomplete resection. RESULTS: A total of 56 patients underwent resection of MGCT. The 5-y progression-free survival (PFS) and overall survival (OS) were 79% and 83%. In multivariate analysis, complete resection was the only significant prognostic factor for better PFS (hazard ratio (HR) = 9.083, P= 0.00021) and OS (HR = 5.519, P= 0.0445). The preoperative CT finding of arteries (including the aorta, right brachiocephalic artery, left common carotid artery, and left subclavian artery) surrounded by the tumor was a predictor of incomplete resection (odds ratio = 10.089, P= 0.049). CONCLUSIONS: Complete resection is essential for improving the survival of MGCT, and the risk stratification using preoperative CT imaging brings important information to achieve the complete resection.

Primary mediastinal germ cell tumours with high prevalence of somatic malignancy: An experience from a single tertiary care oncology centre.

BACKGROUND: Primary mediastinal germ tumours (PMGCT) constitute, a mere 3-4% of all germ cell tumours (GCT). Although they account for approximately 16% of mediastinal tumours in adults and 19-25% in children as per western literature, there is hardly any large series on PMGCT reported from the Indian subcontinent. DESIGN: We have retrospectively analysed clinicopathological features of 98 cases of PMGCT diagnosed over 10 years (2010-2019) from a tertiary-care oncology centre. RESULTS: The study group (n = 98) comprised predominantly of males (n = 92) (M:F ratio-15:1), with an age range between 3 months to 57 years (median: 25 years). The tumours were predominantly located in the anterior mediastinum (n = 96). Broadly, Non-seminomatous germ cell tumours (NSGCT) were more common (n = 73, 74%) compared to pure seminoma (n = 25, 26%). Mixed NSGCT was the most common histological subtype (n = 30) followed by pure mature teratoma (n = 18), pure Yolk sac tumour (n = 13), mixed seminoma and NSGCT (n = 5), pure immature teratoma (n = 3) and GCT; NOS (n = 4). Interestingly, all female patients had exclusive teratomas. Nine cases revealed secondary somatic malignancy (5 carcinomas and 4 sarcomas). The majority of patients received neoadjuvant chemotherapy (n = 71). Surgical excision was performed in 60 patients. Follow up was available in 68 patients. NSGCT showed a poor prognosis as compared to seminoma (p value = 0.03) and tumours with somatic malignancies had a more aggressive clinical course. CONCLUSION: PMGCT was seen predominantly in young adult males and somatic malignancies were noted in as high as 9% of cases. Patient with somatic malignancy have aggressive clinical course, hence, extensive sampling and careful histopathological evaluation are recommended for the identification and definitive characterization.

Assessment of isochromosome 12p and 12p abnormalities in germ cell tumors using fluorescence in situ hybridization, single-nucleotide polymorphism arrays, and next-generation sequencing/mate-pair sequencing.

The identification of isochromosome 12p [i(12p)] and 12p gains have significant clinical utility in the diagnosis of germ cell tumors (GCTs). We have summarized the results of fluorescence in situ hybridization (FISH) assays to identify i(12p), performed in a Clinical Laboratory Improvement Amendments (CLIA)-validated setting for 536 specimens. In addition, the American Association for Cancer Research (AACR) Project GENIE registry and The Cancer Genome Atlas (TCGA) data sets were evaluated for chromosome 12p gains, and a limited number of cases were concurrently evaluated using FISH, single-nucleotide polymorphism (SNP) arrays and next-generation sequencing (NGS; including mate-pair sequencing). Specimens submitted for FISH testing were frequently from potential sites of metastases (male: 70.9% and female: 69.3%), and polysomy of chromosome 12 with or without concurrent i(12p) was a frequent finding, seen in 3% (16/536) and 35% (186/536) of cases, respectively. Our analysis suggests that 12p gains are likely to be present in approximately 73% of male GCT and in 32% of female GCT (AACR GENIE, n = 555). When comparing TCGA cases of testicular GCT (n = 149) to combined cases of sarcoma, colorectal, prostate, and urothelial carcinoma (n = 1754), 12p gains had a sensitivity of 77.2% and specificity of 97.3% for GCT. Some advantages of FISH over SNP arrays/NGS include relatively lower cost, rapid turnaround time, the ability to analyze biopsy material with a limited number of tumor cells (50 cells), and the ability to distinguish i(12p) from polysomy. The ability to spatially restrict the analysis to cells of interest is critical, as specimens submitted for testing often have low tumor purity. Disadvantages include false negative results due to an inability to detect segmental gains due to FISH probe design. With the availability of numerous testing modalities, including FISH, SNP arrays, and NGS-based assays, a nuanced understanding of the advantages and disadvantages of each methodology, as has been presented in this study, may inform appropriate testing strategies.