Objective To determine whether ultrasound imaging can reduce the risk of failed lumbar punctures or epidural catheterisations, when compared with standard palpation methods, and whether ultrasound imaging can reduce traumatic procedures, insertion attempts, and needle redirections.Design Systematic review and meta-analysis of randomised controlled trials. Review methods Randomised trials that compared ultrasound imaging with standard methods (no imaging) in the performance of a lumbar puncture or epidural catheterisation were identified. Data sources
Purpose To risk stratify malignant extracranial pediatric germ cell tumors (GCTs). Patients and Methods Data from seven GCT trials conducted by the Children's Oncology Group (United States) or the Children's Cancer and Leukemia Group (United Kingdom) between 1985 and 2009 were merged to create a data set of patients with stage II to IV disease treated with platinum-based therapy. A parametric cure model was used to evaluate the prognostic importance of age, tumor site, stage, histology, tumor markers, and treatment regimen and estimate the percentage of patients who achieved long-term disease-free (LTDF) survival in each subgroup of the final model. Validation of the model was conducted using the bootstrap method. Results In multivariable analysis of 519 patients with GCTs, stage IV disease (P = .001), age ≥ 11 years (P < .001), and tumor site (P < .001) were significant predictors of worse LTDF survival. Elevated alpha-fetoprotein (AFP) ≥ 10,000 ng/mL was associated with worse outcome, whereas pure yolk sac tumor (YST) was associated with better outcome, although neither met criteria for statistical significance. The analysis identified a group of patients age > 11 years with either stage III to IV extragonadal tumors or stage IV ovarian tumors with predicted LTDF survival < 70%. A bootstrap procedure showed retention of age, tumor site, and stage in > 94%, AFP in 12%, and YST in 27% of the replications. Conclusion Clinical trial data from two large national pediatric clinical trial organizations have produced a new evidence-based risk stratification of malignant pediatric GCTs that identifies a poor-risk group warranting intensified therapy.
BACKGROUND There is a debate regarding the management of ovarian immature teratomas (ITs). In adult women, postoperative chemotherapy is standard except for stage I, grade 1 disease, whereas surgery alone is standard in pediatric patients. To determine the role of chemotherapy, a pooled analysis of pediatric and adult clinical trials was conducted. METHODS Data from 7 pediatric trials and 2 adult trials were merged in the Malignant Germ Cell International Collaborative data set. Four trials included patients with newly diagnosed pure ovarian ITs and were selected (Pediatric Oncology Group/Children’s Cancer Group Intergroup Study (INT 0106), Second UKCCSG Germ Cell Tumor Study (GC2), Gynecologic Oncology Group (GOG 0078 and GOG 0090). Adult and pediatric trials were analyzed separately. The primary outcome measures were event-free survival (EFS) and overall survival (OS). RESULTS One hundred seventy-nine patients were included (98 pediatric patients and 81 adult patients). Ninety pediatric patients were treated with surgery alone, whereas all adult patients received chemotherapy. The 5-year EFS and OS were 91% and 99%, respectively, for the pediatric cohort and 87% and 93%, respectively, for the adults. There were no relapses in grade 1 patients, regardless of the stage or age. Only 1 adult patient with a grade 2 IT relapsed. Among grade 3 patients, the 5-year EFS was 0.92 (0.72–0.98) for stage I/II and 0.52 (0.22–0.75) for stage III in the pediatric cohort (P = .005) and 0.91 (0.69–0.98) for stage I/II and 0.65 (0.39–0.83) for stage III/IV in the adult cohort (P = .01). Postoperative chemotherapy did not decrease relapses in the pediatric cohort. CONCLUSIONS The grade was the most important risk factor for relapse in ovarian ITs. Among grade 3 patients, the stage was significantly associated with relapse. Adjuvant chemotherapy did not decrease relapses in the pediatric cohort; its role in adults remains unresolved.
Dexrazoxane is associated with a statistically significant risk reduction for most cardiotoxic outcomes. Dexrazoxane is associated with a statistically borderline increase in SMNs, possibly because of an interaction with concurrent cancer therapies. The decision to use dexrazoxane in children should balance the risks of cardiotoxicity and SMNs specific to each treatment protocol.
The management of paediatric extracranial germ cell tumours (GCTs) carries a unique set of challenges. GCTs are a heterogeneous group of neoplasms that present across a wide range of age, site, histology, and clinical behaviour. They are managed by a diverse variety of specialists. Correspondingly, their staging, risk-stratification, and treatment approaches have evolved disparately along multiple trajectories. Paediatric GCTs differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate evidence-based care. Suboptimal outcomes remain for several patient groups, and among survivors there are significant long-term toxicities.The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into better patient outcomes. Future trials will be characterised by improved riskstratification systems, biomarkers for response and toxicity, rational reduction of therapy for low-risk patients and novel approaches for highrisk patients, and improved international collaboration across paediatric and adult cooperative research groups. Correspondingly, their staging, risk-stratification, and treatment approaches have evolved disparately along multiple trajectories. Paediatric GCTs differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate evidence-based care.Suboptimal outcomes remain for several patient groups, and among survivors there are significant long-term toxicities. The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into better patient outcomes. Future trials will be characterised by improved risk-stratification systems, biomarkers for response and toxicity, rational reduction of therapy for low-risk patients and novel approaches for high-risk patients, and improved international collaboration across paediatric and adult cooperative research groups.
PTGC is a nonspecific manifestation of a variety of associated conditions. There is a small risk of subsequent HL, and a larger risk of requiring multiple biopsies for recurrent PTGC. The presence of an immune disorder should be considered in patients who present with generalized lymphadenopathy, splenomegaly, immune cytopenias, and/or progression to HL. Routine surveillance imaging may not be required. Future research should determine the optimal surveillance strategy for patients with PTGC and the indications for repeat biopsies.
During the past 35 years, survival rates for children with extracranial malignant germ cell tumors (GCTs) have increased significantly. Success has been achieved primarily through the application of platinum-based chemotherapy regimens; however, clinical challenges in GCTs remain. Excellent outcomes are not distributed uniformly across the heterogeneous distribution of age, histologic features, and primary tumor site. Despite good outcomes overall, the likelihood of a cure for certain sites and histologic conditions is less than 50%. In addition, there are considerable long-term treatment-related effects for survivors. Even modest cisplatin dosing can cause significant long-term morbidities. A particular challenge in designing new therapies for GCT is that a variety of specialists use different risk stratifications, staging systems, and treatment approaches for three distinct age groups (childhood, adolescence, and young adulthood). Traditionally, pediatric cancer patients younger than 15 years have been treated by pediatric oncologists in collaboration with their surgical specialty colleagues. Adolescents and young adults with GCTs often are treated by medical oncologists, urologists, or gynecologic oncologists. The therapeutic dilemma for all is how to best define disease risk so that therapy and toxicity can be appropriately reduced for some patients and intensified for others. Further clinical and biologic insights can only be achieved through collaborations that do not set limitations by age, sex, and primary tumor site. Therefore, international collaborations, spanning different cooperative groups and disciplines, have been developed to address these challenges.
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