Nomograms to predict the prognosis in malignant ovarian germ cell tumors: a large cohort study.

BACKGROUND: Malignant ovarian germ cell tumors (MOGCTs) are rare gynecologic neoplasms. The use of nomograms that are based on various clinical indicators to predict the prognosis of MOGCTs are currently lacking. METHODS: Clinical and demographic information of patients with MOGCT recorded between 2004 and 2015 were obtained from the Surveillance, Epidemiology, and End Results database, and Cox regression analysis was performed to screen for important independent prognostic factors. Prognostic factors were used to construct predictive calculational charts for 1-year, 3-year, and 5-year overall survival (OS). The externally validated case cohort included a total of 121 MOGCT patients whose data were recorded from 2008 to 2019 from the database of the Shengjing Hospital of China Medical University. RESULTS: A total of 1401 patients with MOGCT were recruited for the study. A nomogram was used to forecast the 1-year, 3-year, and 5-year OS using data pertaining to age, International Federation of Gynecology and Obstetrics (FIGO) staging, histological subtype and grade, and surgical type. Nomograms have a more accurate predictive ability and clinical utility than FIGO staging alone. Internal and external validation also demonstrated satisfactory consistency between projected and actual OS. CONCLUSIONS: A nomogram constructed using multiple clinical indicators provided a more accurate prognosis than FIGO staging alone. This nomogram may assist clinicians in identifying patients who are at increased risk, thus implementing individualized treatment regimens.

Global patterns in testicular cancer incidence and mortality in 2020.

With 74 500 new cases worldwide in 2020, testicular cancer ranks as the 20th leading cancer type, but is the most common cancer in young men of European ancestry. While testicular cancer incidence has been rising in many populations, mortality trends, at least those in high-income settings, have been in decline since the 1970s following the introduction of platinum-based chemotherapy. To examine current incidence and mortality patterns, we extracted the new cases of, and deaths from cancers of the testis from the GLOBOCAN 2020 database. In 2020, testicular cancer was the most common cancer in men aged 15 to 44 in 62 countries worldwide. Incidence rates were highest in West-, North- and South-Europe and Oceania (age-standardised rate, ASR ≥7/100 000), followed by North America (5.6/100 000 and lowest (<2/100 000) in Asia and Africa. The mortality rates were highest in Central and South America (0.84 and 0.54 per 100 000, respectively), followed by Eastern and Southern Europe, and Western and Southern Africa. The lowest mortality rates were in Northern Europe, Northern Africa and Eastern Asia (0.16, 0.14, 0.9 per 100 000, respectively). At the country level, incidence rates varied over 100-fold, from 10/100 000 in Norway, Slovenia, Denmark and Germany to ≤0.10/100 000 in Gambia, Guinea, Liberia, Lesotho. Mortality rates were highest in Fiji, Argentina and Mexico. Our results indicate a higher mortality burden in countries undergoing economic transitions and reinforce the need for more equitable access to testicular cancer diagnosis and treatment globally.

Parity is associated with better prognosis in ovarian germ cell tumors, but not in other ovarian cancer subtypes.

Ovarian cancer is influenced by reproductive factors, with a reduced risk of epithelial ovarian cancer in parous women. Nonepithelial ovarian cancer frequently affects young women and often precedes or occurs during the childbearing years. However, the impact of reproductive factors on ovarian cancer survival remains unclear: in epithelial ovarian cancer, data are conflicting, and subtype-specific associations have not been examined, and in nonepithelial ovarian cancer, it has not been studied. Using Swedish registers, we evaluated associations between women's reproductive history and cancer-specific mortality by subtype of epithelial and nonepithelial ovarian cancer in 3791 women born 1953 and later, diagnosed from 1990 to 2018. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated using Cox-proportional hazard models. Parity was associated with a 78% decreased risk of cause-specific mortality in 243 women with germ cell tumors (GCTs) (parous vs nulliparous, adjusted for age at diagnosis: HR: 0.22 [95% CI 0.07-0.62]), with a decreased risk with increasing number of births (per birth: HR: 0.60 [95% CI 0.38-0.95]). We found no evidence of associations between parity and cause-specific mortality among the 334 patients with sex-cord stromal tumors, nor among the 3214 patients with epithelial ovarian cancer; neither overall, nor by subtype. In conclusion, in our large, population-based study, parity was associated with a clearly better prognosis in GCTs but not in the other ovarian cancer subtypes. Future research on how hormone exposure impacts GCT development may lead to a better understanding of mechanisms affecting survival.

Somatic-type Malignancies in Testicular Germ Cell Tumors: A Clinicopathologic Study of 63 Cases.

The development of somatic-type malignancies (SMs) in testicular germ cell tumors (GCTs) is a rare but well-recognized phenomenon. We studied the pathologic features of 63 GCTs with SMs in the testis (n=22) or metastases (n=41) and correlated these features with clinical outcomes. The patients with SMs in the testis (median age, 26 y) were younger than those with metastatic SMs (median age, 38.5 y). The SMs consisted of carcinomas (n=21), sarcomas (n=21), primitive neuroectodermal tumors (n=15), nephroblastomas (n=3), and mixed tumors (n=3). Sarcoma was the most common SM in the testis (n=11), and most sarcomas were rhabdomyosarcomas (n=9). Carcinoma was the most common SM in metastases (n=20), and most carcinomas were adenocarcinomas (n=12). In metastases, carcinomatous SMs developed after a longer interval from the initial orchiectomy (median times, 213 mo) than sarcomatous SMs (median times, 68 mo). Patients with metastatic SMs had significantly poorer overall survival than those with SMs in the testis (5-y survival rate, 35% vs. 87%; P=0.011). Furthermore, patients with carcinomatous SMs had a significantly worse prognosis than those with sarcomatous or primitive neuroectodermal tumor SMs (5-y survival rates, 17%, 77%, and 73%, respectively; P=0.002), when the whole cohort, including testicular and metastatic SMs, were analyzed. Our results demonstrate that SMs in metastatic GCTs are associated with a significantly worse prognosis than those in the testis. Furthermore, the histologic subtype of SM has a significant effect on the clinical outcome, with the carcinomatous SM carrying the highest risk for mortality.

Outcome of Postchemotherapy Residual Disease in Extracranial Germ Cell Tumor in Children: Experience of a Tertiary Care Center.

OBJECTIVES: The aim was to review outcome with residual disease at the end of first line chemotherapy in patients with extracranial germ cell tumor (GCT) in our resource limited setting. METHODS: A retrospective analysis of 196 patients with GCT recruited at Shaukat Khanum Memorial Cancer Hospital (SKMCH) from January 2008 to December 2016. Data fields included site, histopathology, stage, risk groups, baseline alpha fetoprotein, beta human chorionic gonadotropin levels, residuum after primary treatment, completeness of surgical excision and outcomes. Data analysis involved quantitative analysis, mean and median calculations, event free survival (EFS) and overall survival (OS) calculations using Kaplan-Meier curves. RESULTS: In 196 included patients, M:F ratio was 1. There were 81 (41.3%) adolescents. Alpha fetoprotein was >10,000 IU/L in 56 (28.6%) patients. Sixty-two (31.6%) patients had extragonadal disease. Most patients (n=137, 69.9%) presented with advanced stage (III/IV). Seventy-six patients had postchemotherapy residual disease (n=59 [78%] with partial response (PR) and 17 [22%] with no response [NR]). Five-year OS was 83% and EFS was 67%. Five-year EFS of patients with complete remission after primary chemotherapy was 85% versus 70% in patients with PR and 6% in those with NR (P=0.001). OS in patients with complete remission, PR and NR was 94%, 87%, and 46%, respectively. All patients with NR progressed or relapsed and 8/17 died. Four patients with normalized tumor marker response were found to have active tumor on resection of postchemotherapy residuum. CONCLUSION: Patients with postchemotherapy residual disease in pediatric extracranial GCTs, fare better if their residuum is resected compared with those who do not undergo resection.

Clinical phenotypes and prognostic features of embryonal tumours with multi-layered rosettes: a Rare Brain Tumor Registry study.

BACKGROUND: Embryonal tumours with multi-layered rosettes (ETMRs) are a newly recognised, rare paediatric brain tumour with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and scarce clinical data, disease features and determinants of outcomes for these tumours are poorly defined. We did an integrated clinicopathological and molecular analysis of primary ETMRs to define clinical phenotypes, and to identify prognostic factors of survival and key treatment modalities for this orphan disease. METHODS: Paediatric patients with primary ETMRs and tissue available for analyses were identified from the Rare Brain Tumor Consortium global registry. The institutional histopathological diagnoses were centrally re-reviewed as per the current WHO CNS tumour guidelines, using histopathological and molecular assays. Only patients with complete clinical, treatment, and survival data on Nov 30, 2019, were included in clinicopathological analyses. Among patients who received primary multi-modal curative regimens, event-free survival and overall survival were determined using Cox proportional hazard and log-rank analyses. Univariate and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) with 95% CIs for clinical, molecular, or treatment-related prognostic factors. FINDINGS: 159 patients had a confirmed molecular diagnosis of primary ETMRs (median age at diagnosis 26 months, IQR 18-36) and were included in our clinicopathological analysis. ETMRs were predominantly non-metastatic (94 [73%] of 128 patients), arising from multiple sites; 84 (55%) of 154 were cerebral tumours and 70 (45%) of 154 arose at sites characteristic of other brain tumours. Hallmark C19MC alterations were seen in 144 (91%) of 159 patients; 15 (9%) were ETMR not otherwise specified. In patients treated with curative intent, event-free survival was 57% (95% CI 47-68) at 6 months and 31% (21-42) at 2 years; overall survival was 29% (20-38) at 2 years and 27% (18-37) at 4 years. Overall survival was associated with non-metastatic disease (HR 0·48, 95% CI 0·28-0·80; p=0·0057) and non-brainstem location (0·42 [0·22-0·81]; p=0·013) on univariate analysis, as well as with gross total resection (0·30, 0·16-0·58; p=0·0014), high-dose chemotherapy (0·35, 0·19-0·67; p=0·0020), and radiotherapy (0·21, 0·10-0·41; p<0·0001) on multivariable analysis. 2-year event-free and overall survival was 0% at 2 years in patients treated with conventional chemotherapy without radiotherapy (regardless of surgery extent), and 21% (95% CI 1-41) and 30% (6-54), respectively, in patients treated with high-dose chemotherapy, and gross total resection without radiotherapy. 2-year event-free survival in patients treated with high-dose chemotherapy and radiotherapy was 66% (95% CI 39-93) for patients with gross total resection and 44% (7-81) for patients with sub-total resection. 2-5-year overall survival was 66% (95% CI 33-99, p=0·038) for patients with gross total resection and 67% (36-98, p=0·0020) for patients with sub-total resection. INTERPRETATION: Prompt molecular diagnosis and post-surgical treatment with intensive multi-modal therapy tailored to patient-specific risk features could improve ETMR survival. FUNDING: Canadian Institute of Health Research, Canada Research Chair Awards, Australian Lions Childhood Cancer Research Foundation, Spanish Society of Pediatrics, Consejería de Salud y Familias de la Junta de Andalucía, Miracle Marnie, Phoebe Rose Rocks, Tali's Funds, Garron Cancer Centre, Grace's Walk, Meagan's Hug, Brainchild, Nelina's Hope, and Jean Martel Foundation.

Significant improvement in survival of advanced stage childhood and young adolescent cancer in the Netherlands since the 1990s.

BACKGROUND: This is the first national study on trends in cancer survival and mortality for children and young adolescents in the Netherlands including unique information on stage at diagnosis. METHODS: All neoplasms in patients <18 years, diagnosed between 1990 and 2015 (N = 14,060), were derived from the Netherlands Cancer Registry. Cohort and period survival analyses were used to estimate observed survival (OS). Time trends in OS and mortality rates were evaluated by parametric survival models and average annual percentage change, respectively. RESULTS: Between 1990 and 2015, 5-year OS and 10-year OS of childhood and young adolescent cancer have improved significantly by 9 percent points, reaching 81% and 78%, respectively. Favourable trends in survival were observed for all age groups and most diagnostic (sub)groups, being particularly pronounced for advanced disease. Non-Hodgkin lymphomas Ann Arbor stage III, metastatic neuroblastomas (age ≥18 months) and Ewing bone sarcomas showed significant improvements in 5-year OS. Compared with 1990-99, the risk of dying within five years of diagnosis was decreased significantly during 2000-09 (hazard ratio [HR] = 0.8) and 2010-15 (HR = 0.6), after adjustment for age, gender and follow-up time. Nonetheless, the prognosis of young patients suffering from central nervous system tumours, neuroblastoma and osteosarcomas remained modest, with 5-year OS <70% and 10-year OS <65%. Childhood and young adolescent cancer mortality decreased by an average of 2.0% annually between 1990 and 2018. CONCLUSIONS: Significant progress has been realised in the prognosis of childhood and young adolescent cancer in the Netherlands since the 1990s. Survival improvements were especially evident for patients with advanced stages and were also reflected in the declining mortality rates.

Incidence and outcomes of malignant ovarian germ cell tumors in Korea, 1999-2017.

OBJECTIVE: Malignant ovarian germ cell tumor (MOGCT) is a rare ovarian malignancy accounting for less than 5% of all ovarian cancers. We aimed to evaluate the incidence, survival, and subsequent malignancies after the diagnosis of MOGCT. METHODS: Data from the Korea Central Cancer Registry were used to identify MOGCTs between 1999 and 2017. The age-standardized rates (ASRs), 5-year relative survival rates (RSR) and standardized incidence ratio (SIR) for subsequent cancer after diagnosis of MOGCT were estimated. RESULTS: Of 2125 cases of newly diagnosed MOGCTs, 596 (28.0%) were diagnosed with dysgerminoma and 1529 (72.0%) with non-dysgerminoma. The ASR per 100,000 women-years was 0.539; ASR slightly increased over the study period (annual percent change [APC] = 1.01%; p = 0.02). There was an increase and decrease in the incidence of MOGCTs in the age groups 0-19 years (APC = 1.96%; p < 0.01) and ≥ 50 years (APC = -6.51%; p < 0.01), respectively. Patients with dysgerminoma showed significantly higher RSR than patients with non-dysgerminoma (98.0% vs. 94.9%, p < 0.01). Patients aged ≥50 years showed worst 5-year RSR (68.7%) than patients aged 0-19 years (97.8%) and 20-34 years (96.4%) (p < 0.01). The overall SIR for a subsequent cancer occurrence was 2.07, with the most frequent site of subsequent primary cancer being the thyroid (SIR = 2.78). CONCLUSIONS: Our data demonstrated an excellent prognosis of MOGCTs among Korean women. There was a slight increase in MOGCT prevalence, which was more pronounced among those aged <19 years. After MOGCT diagnosis, the risk of developing a subsequent malignancy was doubled compared with the general population.

Frequency and risk factors of bleomycin-induced pulmonary toxicity in South Indian patients with germ-cell tumors.

AIM: Bleomycin, etoposide, and cisplatin (BEP) regimen is the standard treatment for germ-cell tumors (GCTs). Bleomycin-induced pulmonary toxicity (BPT) is fatal and dose-limiting toxicity associated with this regimen. In this study, we aimed to identify the frequency and risk factors of BPT in South Indian GCT patients receiving BEP regimen. PATIENTS AND METHODS: The study was carried out in the Department of Medical Oncology, Regional Cancer Centre at a tertiary care hospital in South India. All the patients with GCT (testicular and ovarian) who were receiving BEP regimen from December 2014 to May 2018 were included in the study. BPT was defined as the presence of radiological features and/or clinical symptoms during or post-treatment. RESULTS: BPT was observed in 11 (27%) patients of 41 analyzed patients. Five (12%) patients developed BPT during treatment whereas six (15%) patients developed BPT post-treatment. Cumulative bleomycin dose ≥240 mg (relative risk 3.8, confidence interval: 1.2-12.2,P =0.02) was found to increase the risk of BPT. Three-year overall survival in patients with and without toxicity was 82% and 93%, respectively. CONCLUSIONS: The frequency of BPT in the study population is 27%, and cumulative bleomycin dose ≥240 mg has been found to be associated with increased risk of developing BPT. BPT does not negatively impact survival outcome in GCT patients receiving BEP regimen.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Toll-like receptor 2 (TLR2) is a candidate prognostic factor in testicular germ cell tumors as well as an indicator of immune function in the tumor microenvironment.

Testicular cancer is the most common malignant tumor in young men, and its incidence has increased in recent years. The tumor microenvironment (TME) plays a crucial role in the development and progression of tumors; however, the TME of testicular germ cell tumor (TGCT) is poorly understood. In this study, we downloaded information for 156 TGCT cases from The Cancer Genome Atlas (TCGA) database, used the ESTIMATE method to determine immune and stromal scores, and used CIBERSORT to calculate the proportion of tumor-infiltrating immune cells (TICs). The differentially expressed genes were subjected to a COX regression analysis and used for the construction of a protein-protein interaction (PPI) network. Toll-like receptor 2 (TLR2) was identified as a predictive marker by combining the results of the Cox regression analysis and PPI network. A survival analysis showed that TLR2 was positively correlated with TGCT survival. A gene set enrichment analysis indicated that genes in the high TLR2 expression group were enriched for cell adhesion molecules (CAMs) and the chemokine signaling pathway, and genes in the low TLR2 expression group were mainly enriched in the spliceosome. Regarding proportions of TICs, naive B cells and follicular helper T cells were negatively correlated with the expression of TLR2. This suggests that as TLR2 expression increases, the immunocompetence of the TME decreases. The expression of TLR2 may affect the prognosis of TGCT, suggesting that this locus can be used as a prognostic factor for TGCT.

Clinicopathological characteristics and outcomes in embryonal tumor with multilayered rosettes: A decade long experience from a tertiary care centre in North India.

BACKGROUND: Embryonal tumor with multilayered rosettes (ETMR) are a heterogenous group clinically, pathologically and topographically. Due to limited cases, data regarding its molecular genetics, pathology and prognostic factors is evolving. We retrospectively analysed our cohort of ETMR over last decade in order to study their clinicopathological characteristics and outcome. METHODS: Our cohort consisted of patients diagnosed with Embryonal tumor with abundant neuropil and true rosettes (ETANTR)/Ependymoblastoma (EBL)/ Medulloepithelioma (MEPL) over the past decade. Clinical details, including outcome and imaging data was retrieved. Histological analysis including immunohistochemical work-up was performed. RESULTS: Cohort included 15 patients with age range between 1 and 28 years and M:F ratio of 1.5:1. Supratentorial location predominated in comparison to tumors arising in posterior fossa. ETANTR and EBL patterns were equally distributed (40% each), followed by one case each of mixed pattern (EBL + ETANTR), MEPL and embryonal tumor, unclassified. All tumors readily expressed LIN 28A and INI-1 was retained. Recurrence with evidence of glial and rhabdoid differentiation was noted in a single patient 9 months following resection. Follow-up period ranged from 1 to 31 months, with overall median survival of 6.4 months. Eight patients were planned for adjuvant treatment following surgery, of which only four could complete it. All patients, except for one, succumbed to the disease. CONCLUSIONS: ETMR have a heterogenous morphology and gathers ETANTR, EBL, MEPL within its spectrum. Following treatment, the recurrent tumor may feature glial/rhabdoid differentiation. LIN28A is expressed in all cases, however should be interpreted in context of histology. Prognosis of ETMR remains dismal despite multimodal therapy.

Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium.

PURPOSE: The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. MATERIALS AND METHODS: Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set. RESULTS: Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided (https://www.eortc.org/IGCCCG-Update). CONCLUSION: The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.

Assessment of Prognostic Factors of Racial Disparities in Testicular Germ Cell Tumor Survival in the United States (1992-2015).

OBJECTIVE: Testicular germ cell tumors (TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed. METHODS: The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT. RESULTS: Black males were diagnosed at a later stage, more commonly with local or distant metastases. The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival (OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality. CONCLUSION: Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.

Screening for cancers with a good prognosis: The case of testicular germ cell cancer.

BACKGROUND: To determine, using testicular germ cell cancer screening as an example, whether screening can also be effective for cancers with a good prognosis. METHODS: Based on the Dutch incidence, stage distribution, and survival and mortality data of testicular germ cell cancer, we developed a microsimulation model. This model simulates screening scenarios varying in screening age, interval, self-examination or screening by the general practitioner (GP), and screening of a defined high-risk group (cryptorchidism). For each scenario, the number of clinically and screen-detected cancers by stage, referrals, testicular germ cell cancer deaths, and life-years gained were projected. RESULTS: Annual self-examination from age 20 to 30 years resulted in 767 cancers detected per 100,000 men followed over life-time, of which 123 (16%) by screening. In this scenario, 19.2 men died from the disease, 4.7 (20%) less than without screening, and 230 life-years were gained. Around 14,000 visits to the GP and 2080 visits to an urologist were required. This scenario resulted in the most favorable ratio between extra visits to the GP or urologist and deaths prevented (1418 and 116 respectively). Monthly screening, or screening until age 40 resulted in less favorable ratios. Self-examination by only the high-risk population prevented 1.0 death per 100,00 men in the general population. In all scenarios, 46-50 life-years were gained for each testicular germ cell cancer death prevented. CONCLUSION: Despite the good prognosis, self-examination at young ages for testicular germ cell cancer could be considered.

Embryonal tumors with multilayered rosettes: A tertiary care centre experience.

BACKGROUND: Embryonal tumors with multilayered rosettes (ETMR) is an extremely rare and highly aggressive tumor. It includes three distinct entities i.e, embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL) and medulloepithelioma (MEPL). Here, we present our institutional experience of seven ETMR cases treated over a period of five years. MATERIALS AND METHODS: Patients' records from 2015 to 2019 were reviewed manually and electronically to retrieve the data. Clinicopathological and outcome details of ETMR cases were entered in a predesigned proforma. RESULTS: A total of seven cases of ETMR were registered from 2015 to 2019 with a median age at presentation of four years (range 3-7 years). All patients underwent surgery. However, only three patients completed the planned adjuvant treatment, comprising of focal radiotherapy (RT) alone, craniospinal irradiation (CSI) alone and CSI followed by six cycles of chemotherapy in one patient each respectively. Two patients commenced CSI but deteriorated during RT and thereafter needed best supportive care. Two patients could not be started on any adjuvant treatment. Unfortunately, six patients succumbed to their disease within one year of their diagnosis. Only one patient who received both CSI and adjuvant chemotherapy is alive at 15 months of diagnosis. CONCLUSION: ETMR is a rare and aggressive entity. Majority of the patients die within one year of the diagnosis despite multimodality treatment.

Lymph Node Ratio Rather Than Positive Lymph Node Counts Has Better Prognostic Value in Patients With Testicular Germ Cell Tumors.

BACKGROUND: Testicular cancer represents the most common malignancy in young adult men. In the current study, we sought to analyze and compare the prognostic value of lymph node ratio (LNR) as well as positive lymph node counts (LNC) to understand its clinical significance in testicular germ cell tumors. METHODS: We employed eligibility criteria to recruit a total of 931 patients, with testicular cancer, from 2010 to 2015 from The Surveillance, Epidemiology, and End Results (SEER) database. We then used the X-Tile program to calculate LNR and LNC cutoff values and discriminate survival. We then calculated the overall and cancer specific survival rates and analyzed the association between LNR/LNC and clinical pathological characteristics using the χ2 test. Finally, we assessed the relationships between clinical pathological factors and patient survival using univariate Cox proportional hazard analysis. RESULTS: Univariate analysis revealed a significant association between prognosis with age (HR, 5.169; 95% CI, 1.758-15.200; P = 0.003), AJCC stage (III vs I: HR, 9.298; 95% CI, 2.691-32.131; P < 0.001), M stage (HR, 7.897; 95% CI, 3.417-18.251; P < 0.001) and LNR (HR, 3.009; 95% CI, 1.275-7.098; P = 0.012). On the other hand, LNC (HR, 1.743; 95% CI, 0.687-4.420; P = 0.242) was not significantly associated with prognosis. Analysis of the association between LNR/LNC and clinical pathological characteristics showed that high LNR patients tended to have significantly larger tumor sizes (χ2 = 7.877, P = 0.005), as well as advanced T (χ2 = 13.195, P = 0.004), N ( χ2 = 86.775, P < 0.001), M (χ2 = 19.948, P < 0.001) and 7th AJCC (χ2 = 103.074, P < 0.001) stages. In addition, high LNC patients were significantly associated with T (χ2 = 8.799, P = 0.032), N (χ2 = 74.390, P < 0.001) and 7th AJCC (χ2 = 111.759, P < 0.001) stages. CONCLUSION: LNR was a better predictor for long-term prognosis and was closely associated with clinical pathological characteristics than LNC in patients with testicular germ cell tumors.

Multimodality treatment for Central Nervous System Germ Cell Tumors: Disease spectrum and management strategies - A tertiary care center experience from India.

OBJECTIVE: Intracranial germ cell tumors (GCTs) are relatively rare neoplasms, representing 2-3 % of paediatric brain tumors in Western countries and 8-15 % in East Asia. Here, we discuss the clinical features and treatment outcomes in patients with central nervous system (CNS) GCTs treated at our institute. METHODS: Medical records of all primary CNS GCT patients were retrieved retrospectively from 2007 to 2019. Demographic, clinical, treatment and follow up details were entered in a predesigned proforma. Overall survival (OS) and progression-free survival was computed using Kaplan-Meier method and Log-Rank test. Effect of various prognostic factors on survival outcomes was assessed by univariate and multivariate analysis. RESULTS: A total of 28 CNS GCT patients were included in this analysis. Median age at presentation was 17 years (range, 7-45 years) with a male to female ratio of 1.8:1. Pineal region was the commonest location, encountered in 15 patients (53.6 %). Pure germinoma was the most frequent histology observed, seen in 19 patients (67.9 %). Male gender and germinoma histology were highly associated with pineal location (p = 0.043 and p = 0.052, respectively). Fourteen patients underwent surgical intervention and nine patients underwent biopsy for diagnostic purpose or to relieve the obstructive symptoms. Only 23 patients (82.1 %) received chemotherapy. However, all patients received radiotherapy (Craniospinal irradiation/whole brain radiotherapy/whole ventricular radiotherapy/ or local radiotherapy). After a median follow-up of 53 months (range, 7-150), 23 patients (82.1 %) were alive. OS was significantly affected by histology (89 % in germinoma vs. 60 % in non-germinomatous, p = 0.054) and location (93 % in pineal region vs. 64.2 % in other location, p = 0.042). Age, gender and surgery did not have any impact on the survival outcomes. CONCLUSION: CNS GCTs are relatively rare and heterogeneous neoplasms commonly seen in pineal and suprasellar locations. A combination of chemotherapy and radiotherapy had shown excellent outcomes.

Racial and socioeconomic disparities in retroperitoneal lymph node dissection and survival in nonseminomatous germ cell tumor: A population-based study.

BACKGROUND: Though testicular cancer is the most common cancer in young men, there is a paucity of epidemiologic studies examining sociodemographic disparities in adjuvant therapy and outcomes. We examined the associations of sociodemographic factors with retroperitoneal lymph node dissection (RPLND) and survival among patients with nonseminomatous germ cell tumors (NSGCTs). METHODS: Within the Surveillance Epidemiology and End Results database (2005-2015), we identified 8,573 patients with nonseminomatous germ cell tumors. Multivariable logistic regression and Fine-Gray competing-risks regression models were constructed to examine the association of sociodemographic factors (neighborhood SES (nSES), race, and insurance) with, respectively, adjuvant RPLND within 1 year of diagnosis and cancer-specific mortality. RESULTS: Patients in the lowest nSES quintile (OR 0.59, 95% CI = 0.40-0.88, P = 0.01) and Black patients (OR 0.41, 95% CI = 0.15-1.00, P= 0.058) with stage II disease were less likely to receive RPLND compared to those in the highest quintile and White patients, respectively. Stage III patients with Medicaid (OR 0.64, 95% CI = 0.46-0.89, P= 0.009) or without insurance (OR 0.46, 95% CI = 0.27-0.76, P= 0.003) were less likely to receive RPLND compared to patients with private insurance. Lowest quintile nSES patients of all disease stages and Black patients with stage I disease (HR = 2.64, 95% CI = 1.12-6.20, P = 0.026) or stage II disease (HR=4.93, 95% CI = 1.48-16.44, P = 0.009) had higher risks of cancer-specific mortality compared to highest quintile nSES and White patients, respectively. CONCLUSIONS: This national study found multilevel, stage-specific sociodemographic disparities in receipt of RPLND and survival.

Surgical Management of Cervical Non-seminomatous Germ Cell Tumor Metastases.

OBJECTIVE/HYPOTHESIS: Testicular cancer is the most common malignancy of young males. Limited reports describe perioperative and long-term outcomes after surgical resection of metastatic, cervical, non-seminomatous germ cell tumors (NSGCT). The objective of this study was to investigate the effectiveness and safety of cervical lymphadenectomy in the management of metastatic NSGCT. STUDY DESIGN: Retrospective case series. METHODS: A single institution, retrospective review from 1998 to 2020 of patients with metastatic NSGCT who underwent cervical lymphadenectomy was conducted. Clinicopathological, surgical, and postoperative data were collected and analyzed. RESULTS: Sixty-eight predominantly white (91.0%) male patients with mean age 33.0 ± 11.3 years were included. Most (82.2%) presented with stage III disease at initial diagnosis. All patients had undergone primary platinum-based chemotherapy 1.0 to 22.7 months prior to selective ND. Surgery mainly involved nodal levels III (67.6%), IV (92.6%) and/or Vb (77.9%) and was frequently performed with concomitant thoracoabdominal NSGCT resections (63.2%). Cervical specimens predominantly revealed mature teratoma (83.8%) as solitary (69.1%) or component of mixed (14.7%) NSGCT. Ten (14.7%) perioperative complications occurred as vocal cord paresis (n = 6) from thoracic surgery and chyle leakage (n = 4). All resolved conservatively except two vocal cord paralyzes that required surgical repair due to tumor involvement of vagus nerve. Six instances of cervical recurrence occurred at median 12.5 (range, 5.8-38.6) months from ND, all re-demonstrating purely mature teratoma. The two-year cervical, non-cervical, and overall recurrence-free survivals were 83%, 55%, and 55%, respectively. Two-year disease-free and overall survivals were both 93%. CONCLUSIONS: Selective neck dissection is a safe, effective method for managing cervical NSGCT metastases. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1528-1534, 2021.