A pragmatic diagnostic approach to primary intracranial germ cell tumors and their treatment outcomes

Background: Primary intracranial germ cell tumors (ICGCT) are often diagnosed with tumor markers and imaging, which may avoid the need for a biopsy. An intracranial germ cell tumor with mild elevation of markers is seldom stratified as a distinct entity. Methods: Fifty-nine patients were stratified into three groups: pure germinoma (PG), secreting germinoma (SG) and non-germinomatous germ cell tumors (NGGCTs). Results: At 5 years, progression-free survival and overall survival of the three groups (PG vs SG vs NGGCT) were 91% versus 81% versus 59%, and 100% versus 82% versus 68%, respectively. There was no statistically significant difference in outcome among histologically and clinically diagnosed germinomas. Conclusion: A criterion for clinical diagnosis when a biopsy is not feasible is elucidated, and comparable outcomes were demonstrated with histologically diagnosed germinomas.

MicroRNA-profiling of miR-371~373- and miR-302/367-clusters in Serum and Cerebrospinal Fluid Identify Patients with Intracranial Germ Cell Tumors

Purpose: Intracranial germ cell tumors (iGCT) comprise germinoma and non-germinoma. Their diagnosis predominantly relies on biopsy as only one-fifth of patients present with elevated biomarkers (AFP/ß-HCG) in serum or cerebrospinal fluid (CSF). MicroRNAs (miR/miRNA) have emerged as non-invasive biomarkers in extracranial GCT and may potentially facilitate non-invasive diagnosis in iGCT. Methods: We analyzed eight miRNAs in serum and CSF from the miR-371~373- and miR-302/367-clusters and four miRNAs differentially expressed in iGCT tissue (miR-142-5p/miR-146a-5p/miR-335-5p/miR-654-3p) from eight iGCT patients (age 10-33 years) and 12 control subjects by pre-amplified RT-qPCR. MiR-30b-5p (serum) and miR-204-5p (CSF) acted as reference genes. ΔCt-values were expressed as 2-ΔΔCt after standardization against controls. Results: Between iGCT and control patients’ serum ΔCt-values of miR-371a-3p (p=0.0159), miR-372-3p (p=0.0010), miR-367 (p=0.0190), miR-302a (p=0.0381) and miR-302d-3p (p=0.0159) differed significantly. Discriminatory pattern in CSF was similar to serum as miR-371a (p=0.0286), miR-372-3p (p=0.0028), miR-367-3p (p=0.0167) and miR-302d-3p (p=0.0061) distinguished between patients and controls. Abundant 2-ΔΔCt levels of each miRNA were found across all serum and CSF samples including biomarker-negative patients.Conclusion: With the largest data set so far, we underline the suitability of miR-371a, miR-372, miR-367 and miR-302d in serum and CSF for diagnosis of iGCT, particularly in biomarker-negative germinoma. Diagnosis of iGCT by miRNA analysis is a feasible and valid approach, particularly as serum can be readily obtained by a less invasive procedure. MiRNA analysis may discriminate iGCT from other tumors with similar radiological findings and may allow to monitor response to therapy as well as early relapse during follow-up.

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

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

EPID-15. AGE AND DOSIMETRIC IMPACTS ON RADIOTHERAPY ASSOCIATED GROWTH IMPAIRMENT FOR PATIENTS WITH INTRACRANIAL GERM CELL TUMORS (GCTs)

PURPOSE Intracranial germ cell tumors (GCTs) are rare pediatric central nervous system (CNS) tumors. Growth impairment induced by radiation treatments was rarely evaluated. We aimed to study the impacts of radiotherapy on height development and identify the dosimetric constraints. MATERIALS AND METHODS A total of 148 pediatric patients diagnosed with GCTs were retrospectively analyzed. Sex, age at irradiation, physical doses and biologically effective dose (BED), height, and endocrine status were obtained from patient records. The cumulative change in height was assessed using age-matched normalized height (ANH). Variables were assessed for correlations and statistical significance. RESULTS Cumulative physical doses and BEDs for the whole brain and pituitary were derived via DVHs and BEDVHs. In contrast to patients >11.5 yr, linear correlations between ANH and cumulative physical doses as well as BEDs to the whole brain and pituitary were identified in patients≤11.5 yr. Dosimetric constrains to the pituitary was 36 Gy for physical dose (AUC=0.70 [95% CI, 0.54-0.86], P< 0.05) and 63 Gy2 BED (AUC=0.69 [95% CI, 0.53-0.86], P< 0.05). Intriguingly, no significant differences in ANH were found among different CSI dose groups in patients ≤11.5 yr. (all P>0.05). Impaired hormone secretions in terms of GH and TSH were identified following cranial irradiation (both P< 0.001), particularly for those with tumors at the suprasellar region (GH: P< 0.01, TSH: P< 0.001). CONCLUSION Our study revealed the impacts of age, dosimetrics and tumor locations for growth impairment. This study will contribute to the optimization of radiation treatment planning and facilitate more individualized therapeutic strategies in pediatric patient with GCTs.

Right occipital transtentorial approach for a pineal malignant germ cell tumor

Germ cell tumors account for up to 53% of the malignant lesions found in the pineal region and are typically managed with a combination of radiation therapy and chemotherapy. Malignant somatic transformation of intracranial germ cell tumors is exceedingly rare and has only been reported on two other occasions. Here the authors present the case of a pineal yolk sac tumor that failed optimum first-line treatment and underwent malignant somatic transformation to an enteric mucinous adenocarcinoma requiring surgical intervention. This video demonstrates the technical nuances of the occipital transtentorial approach and the safe microsurgical dissection of lesions within the pineal region. The video can be found here: https://stream.cadmore.media/r10.3171/2021.4.FOCVID2151.

GERM-04. PRIMARY INTRACRANIAL GERM CELL TUMORS ARE MORE PREVALENT AMONG PEDIATRIC PATIENTS OF ASIAN/PACIFIC ISLANDER RACE/ETHNICITY IN THE UNITED STATES

Introduction Primary intracranial germ cell tumors (GCTs) appear to be more prevalent among pediatric patients in eastern Asia than in the U.S. Herein we use cancer registry data to evaluate whether GCT prevalence differs by race/ethnicity among U.S. pediatric patients. Methods Pediatric patients (age≤14) presenting between 2004–2017 with a primary intracranial GCT were identified by ICD-O-3 histological and topographical coding from the National Cancer Database (comprising >70% of cancers newly-diagnosed cancers in the U.S.), and categorized by NICHD age stages. Patients’ age, sex, race/ethnicity, and overall survival, and tumor location and size were evaluated. Results 889 pediatric patients with primary intracranial GCTs were identified, which were overwhelmingly male (64.8%) and pure germinomas (64.0%). Non-germinomatous (24.5%) and mixed (11.5%) tumor types were in the minority. Overall, primary GCTs comprised 4.9% of intracranial tumors in pediatric males and 2.9% of intracranial tumors in pediatric females. Asian/Pacific Islander pediatric patients in the U.S. had a notably higher prevalence of GCTs: among Asian/Pacific Islander males, 10.6% of all brain tumors were GCTs, compared to only 4.5% in White non-Hispanic patients, 2.8% in Black non-Hispanic patients, and 6.0% in Hispanic patients. Despite the much lower prevalence of GCTs among female patients overall, this predominance also persisted for Asian/Pacific Islander females, among whom 7.5% of brain tumors were GCTs, compared to only 2.5% in White non-Hispanic patients, 2.4% in Black non-Hispanic patients, and 4.1% in Hispanic patients. Overall, 9.4% of pediatric primary intracranial GCTs occurred in patients of Asian/Pacific Islander race/ethnicity, in contrast to 4.0% of diffuse astrocytic/oligodendroglial tumors, 2.8% of other astrocytic tumors, or 4.6% of embryonal tumors. Conclusions Primary intracranial GCTs affect a substantially larger proportion of both male and female pediatric patients of Asian/Pacific Islander race/ethnicity in the United States.

Precise detection of the germinomatous component of intracranial germ cell tumors of the basal ganglia and thalamus using placental alkaline phosphatase in cerebrospinal fluid

Purpose: The disadvantages of biopsy for lesions in the basal ganglia and thalamus include a risk of various complications, difficulty in selecting the target tissue in some cases due to indistinct neuroimaging findings and limited availability of sample tissue. Placental alkaline phosphatase (PLAP) plays a decisive role in the diagnosis and management of intracranial germ cell tumors (IGCTs) in the basal ganglia and thalamus. The present study aimed to demonstrate the ability, specificity, and optimal use of PLAP values obtained from cerebrospinal fluid (CSF).Methods: Twenty patients with lesions in the basal ganglia and thalamus were enrolled in this study: 11 had IGCTs and 9 had non-IGCTs. The values of PLAP and other established tumor markers in the CSF were measured in all patients before treatment.Results: The mean follow-up period was 76.0 months (range, 3–168) for all lesions. PLAP was elevated in all 11 patients with IGCTs in the basal ganglia or thalamus, whereas none of the patients with non-IGCT exhibited elevated PLAP. Thus, the sensitivity and specificity of PLAP were both 100%.Conclusion: Our data demonstrated that the PLAP value can specifically identify the germinomatous component even in cases of IGCTs in the basal ganglia or thalamus with high sensitivity and specificity. PLAP is undoubtedly beneficial for the safe and timely detection of the germinomatous component of IGCTs in the basal ganglia and thalamus, because reliance on PLAP measurement enables us to avoid invasive surgical procedures and facilitates the prompt initiation of chemoradiation therapy.