Outcomes of intracranial non-germinomatous germ cell tumors: a retrospective Asian multinational study on treatment strategies and prognostic factors.

PURPOSE: Non-germinomatous germ cell tumors (NGGCTs) are rare pediatric conditions. This multicenter study using Asian multinational patient data investigated treatment outcomes and prognostic factors for NGGCTs. METHODS: Medical records of 251 patients with NGGCTs treated from 1995 to 2015 were retrospectively analyzed from participating centers in Asian countries (Korea, Taiwan, Singapore, and Japan). RESULTS: The median follow up was 8.5 years (95% CI 7.8-9.9). In the total cohort, 5-year event-free survival (EFS) and overall survival (OS) rates were 78.2% and 85.4%, respectively. In 17.9% of the patients, diagnosis was determined by tumor markers alone (alpha-fetoprotein ≥ 10 ng/mL (Korea) or > 25 ng/mL (Taiwan and Singapore), and/or ß-human chorionic gonadotropin (ß-hCG) ≥ 50 mIU/mL). Patients with immature teratomas and mature teratomas comprised 12.0% and 8.4%, respectively. The 5-year EFS rate was higher in patients with histologically confirmed germinoma with elevated ß-hCG (n = 28) than those in patients with malignant NGGCTs (n = 127). Among malignant NGGCTs, patients with choriocarcinoma showed the highest 5-year OS of 87.6%, while yolk sac tumors showed the lowest OS (68.8%). For malignant NGGCT subgroups, an increase in serum ß-hCG levels by 100 mIU/mL was identified as a significant prognostic factor associated with the EFS and OS. CONCLUSION: Our result shows excellent survival outcomes of overall CNS NGGCT. However, treatment outcome varied widely across the histopathologic subgroup of NGGCT. Hence, this study suggests the necessity for accurate diagnosis by surgical biopsy and further optimization of diagnosis and treatment according to the histopathology of NGGCTs. Future clinical trials should be designed for individualized treatments for different NGGCTs subsets.

Outcomes of intracranial germinoma-A retrospective multinational Asian study on effect of clinical presentation and differential treatment strategies.

BACKGROUND: This multinational study was conducted to report clinical presentations and treatment strategies in patients with intracranial germinomas across selected Asian centers, including failure patterns, risk factors, and outcomes. METHODS: A retrospective data collection and analysis of these patients, treated between 1995 and 2015 from eight healthcare institutions across four countries was undertaken. RESULTS: From the results, 418 patients were analyzed, with a median follow-up of 8.9 years; 79.9% of the patients were M0, and 87.6% had ß-human chorionic gonadotropin values <50 mIU/mL. The 5/10-year overall survival (OS) and recurrence-free survival (RFS) rates were 97.2%/96.2% and 89.9%/86.9%, respectively. RFS was predicted by the radiotherapy (RT) field, with focal RT having the worst outcome, whereas chemotherapy usage had no impact on survival. Among patients who received chemotherapy, response to chemotherapy did not predict survival outcomes. In M0 patients, primary basal ganglia tumors predicted a worse RFS. In patients with bifocal tumors, an extended field RT was associated with better outcomes. In multivariable analysis, only RT fields were associated with RFS. In relapsed patients, salvage rates were high at 85.7%. Additionally, patients who received salvage RT had a better outcome (91.6% vs. 66.7%). CONCLUSIONS: Survival outcomes of patients with germinoma were excellent. Thus, the focus of treatment for intracranial germinoma should be on survivorship. Further studies are warranted to find the optimal intensity and volume of radiation, including the role of chemotherapy in the survival of patients with intracranial germinomas, considering age, primary tumor location, and extent of disease.

Critical illness epidemiology and mortality risk in pediatric oncology.

OBJECTIVE: Pediatric oncology patients admitted to the pediatric intensive care unit (PICU) are at high risk of mortality. This study aims to describe the epidemiology of and the risk factors for mortality in these patients. STUDY DESIGN: This is a retrospective cohort study including all consecutive PICU oncology admissions from 2011 to 2017. Demographic and clinical risk factors between survivors and nonsurvivors were compared. Both univariate and multivariate Cox proportional hazard regression models were used to quantify the association between 60-day mortality and admission categories, accounting for other covariates (Pediatric Risk Of Mortality [PRISM] III score and previous bacteremia). MAIN OUTCOME MEASURES: The primary outcome was 60-day mortality. RESULTS: The median (interquartile range) age and PRISM III scores of pediatric oncology patients admitted to the PICU were 7 (3, 12) years and 3 (0, 5), respectively. The most common underlying oncological diagnoses were brain tumors (73/200 [36.5%]) and acute lymphoblastic leukemia (36/200 [18.0%]). Emergency admissions accounted for approximately half of all admissions (108/200 [54.0%]), including cardiovascular (24/108 [22.2%]), neurology (24/108 [22.2%]), respiratory (22/108 [20.4%]), and "other" indications (38/108 [35.2%]). The overall 60-day mortality was 35 of 200 (17.5%). Independent risk factors for mortality were emergency respiratory and neurology categories of admission (adjusted hazard ratio[aHR]: 5.62, 95% confidence interval [95% CI]: 1.57, 20.19; P = .008 and aHR: 6.96, 95% CI: 2.04, 23.75; P = .002, respectively) and previous bacteremia (aHR: 3.37, 95% CI: 1.57, 7.20; P = .002). CONCLUSION: Emergency respiratory and neurology admissions and previous bacteremia were independent risk factors for 60-day mortality for pediatric oncological patients admitted to the PICU.

Clinical relevance of screening checklists for detecting cancer predisposition syndromes in Asian childhood tumours.

Assessment of cancer predisposition syndromes (CPS) in childhood tumours is challenging to paediatric oncologists due to inconsistent recognizable clinical phenotypes and family histories, especially in cohorts with unknown prevalence of germline mutations. Screening checklists were developed to facilitate CPS detection in paediatric patients; however, their clinical value have yet been validated. Our study aims to assess the utility of clinical screening checklists validated by genetic sequencing in an Asian cohort of childhood tumours. We evaluated 102 patients under age 18 years recruited over a period of 31 months. Patient records were reviewed against two published checklists and germline mutations in 100 cancer-associated genes were profiled through a combination of whole-exome sequencing and multiplex ligation-dependent probe amplification on blood-derived genomic DNA. Pathogenic germline mutations were identified in ten (10%) patients across six known cancer predisposition genes: TP53, DICER1, NF1, FH, SDHD and VHL. Fifty-four (53%) patients screened positive on both checklists, including all ten pathogenic germline carriers. TP53 was most frequently mutated, affecting five children with adrenocortical carcinoma, sarcomas and diffuse astrocytoma. Disparity in prevalence of germline mutations across tumour types suggested variable genetic susceptibility and implied potential contribution of novel susceptibility genes. Only five (50%) children with pathogenic germline mutations had a family history of cancer. We conclude that CPS screening checklists are adequately sensitive to detect at-risk children and are relevant for clinical application. In addition, our study showed that 10% of Asian paediatric solid tumours have a heritable component, consistent with other populations.

Primary Bone Anaplastic Large Cell Lymphoma Masquerading as Ewing Sarcoma: Diagnosis by Anchored Multiplex PCR.

A 3-year-old boy presented with pathologic fracture of the left proximal femur. Magnetic resonance imaging revealed an aggressive expansile bony mass associated with cortical destruction and surrounding myositis. Computed tomography-guided biopsy revealed a monomorphic small round blue cell tumor by histology. CD99 immunoreactivity and low-level EWSR1 gene translocation by break-apart fluorescent in situ hybridization initially favored a diagnosis of Ewing sarcoma and chemotherapy commenced. Subsequent molecular evaluation by an anchored multiplex polymerase chain reaction-based assay (Archer FusionPlex Sarcoma Panel) revealed a nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) gene fusion. The diagnosis was then amended to primary bone ALK-positive anaplastic large cell lymphoma and the chemotherapy regimen was modified accordingly. This report illustrates the value of this molecular assay in establishing the correct diagnosis of a very rare malignancy masquerading as another tumor type.