Characterizing Lymphovascular Invasion in Pediatric and Adolescent Malignant Ovarian Nongerminomatous Germ Cell Tumors: A Report from the Children's Oncology Group.

BACKGROUND: Lymphovascular invasion (LVI) has been identified as a poor prognostic factor for a variety of tumors; however, its significance in malignant ovarian germ cell tumors (MOGCT) in pediatric and adolescent patients is not well described. We aim to clarify the significance of LVI in the subset of patients with nongerminomatous MOGCT. METHODS: Records of patients 0-20 years of age with MOGCT enrolled on Children's Oncology Group study AGCT0132 were reviewed. Patients with documented presence or absence of LVI in either institutional or central review pathology reports were included. RESULTS: Of 130 patients with MOGCTs, 83 patients had of the presence or absence of LVI documented in their pathology report. 42/83 patients (50.6%) were found to have LVI present. The estimated odds of having LVI was higher in patients with stage II and III disease, 11 years and older and with the presence of choriocarcinoma. Event-free survival (EFS) and overall survival (OS) remained high in patients with LVI. Approximately 50% of patients with a documented LVI status in either institutional pathology report or central review were found to have LVI. CONCLUSIONS: The presence of LVI was higher in tumors with adverse risk factors including higher stage and age greater than 11 years. While LVI was not associated with EFS or OS in the intermediate risk group, further work is necessary to determine the effect of LVI on long-term disease-free survival. We, therefore, recommend routinely incorporating LVI status into institutional pathology reports for pediatric and adolescent patients with MOGCT. LEVEL OF EVIDENCE: III.

Adjuvant chemotherapy does not improve outcome in children with ovarian immature teratoma: A comparative analysis of clinical trial data from the Malignant Germ Cell International Consortium.

BACKGROUND/OBJECTIVES: Surgery is the mainstay of therapy for children with ovarian immature teratoma (IT), whereas adults receive adjuvant chemotherapy, except those with stage-I, grade-1 disease. In Brazil, children with metastatic ovarian IT received postoperative chemotherapy. This practice variation allowed evaluation of the value of chemotherapy, by comparison of Brazilian patients with those in the United States and United Kingdom. DESIGN/METHODS: From the Malignant Germ Cell International Consortium data commons, data on ovarian IT patients from two recently added Brazilian trials (TCG-99/TCG-2008) were compared with data from US/UK (INT-0106/GC-2) trials. Primary outcome measure was event-free (EFS) and overall survival (OS). RESULTS: Forty-two Brazilian patients were included (stage I: 27, stage II: 4, stage III: 8, stage IV: 3). Twenty-nine patients had surgery alone, whereas 13 patients received postoperative chemotherapy. The EFS and OS for entire cohort was 0.80 (95% CI: 0.64-0.89) and 0.97 (0.84-0.99). There was no difference in relapse risk based on stage, grade, or receipt of chemotherapy. Comparing the Brazilian cohort with 98 patients in US/UK cohort (stage I: 59, stage II: 12, stage III: 27), there was no difference in EFS and OS across all stages, despite 87% of stage II-IV Brazilian patients receiving postoperative chemotherapy compared with only 13% of US/UK patients. The EFS and OS for Brazilian compared with US/UK cohort was stage I: 88% versus 98% (p = .05), stage II-IV EFS: 67% versus 79% (p = .32), stage II-IV OS: 93% versus 97% (p = .44); amongst grade-3 patients, there was no difference in EFS or OS. CONCLUSION: Addition of postoperative chemotherapy did not improve outcome in children with ovarian IT, even at higher grade or stage, compared with surgery alone.

A Randomized Controlled Trial of Interventions for Growth Suppression in Children With Attention-Deficit/Hyperactivity Disorder Treated With Central Nervous System Stimulants.

OBJECTIVE: To examine the impact of central nervous system (CNS) stimulants on the growth of children with attention-deficit/hyperactivity disorder (ADHD), and to assess the efficacy and feasibility of weight recovery interventions on growth. METHOD: A total of 230 children aged 5 to 12 years with ADHD with no history of chronic CNS stimulant use were randomly assigned to receive daily CNS stimulants (78%, primarily osmotic release oral system-methylphenidate [OROS-MPH]) or behavioral treatment (22%) for 30 months. After 6 months, children evidencing a decline in body mass index (BMI) of >0.5 z-units were randomized to 1 of 3 weight recovery treatments (WRTs): monthly monitoring of height/weight (MON) plus continued daily medication; drug holidays (DH) with medication limited to school days; or daily caloric supplementation (CS) with a 150-kcal supplement plus daily medication. RESULTS: Before WRT assignment, medication was associated with significant reductions in standardized weight and height (p values <.01). Adherence to CS and DH during WRT was high, with significant increases in daily caloric intake and decreases in weekly medication exposure (p values <.05). Across all WRT participants (n = 71), weight velocity increased significantly after WRT randomization (ß2 = 0.271, SE = 0.027, p < .001).When analyzed by what parents did (versus what they were assigned to), CS (p < .01) and DH (p < .05) increased weight velocity more than MON. No increase in height velocity was seen after randomization to any WRT. Over the entire study, WRT participants declined in standardized weight (-0.44 z-units) and height (-0.20 z-units). CONCLUSION: Drug holidays, caloric supplementation, and increased monitoring all led to increased weight velocity in children taking CNS stimulants, but none led to increased height velocity. CLINICAL TRIAL REGISTRATION INFORMATION: Novel Approach to Stimulant Induced Weight Suppression and Its Impact on Growth; https://clinicaltrials.gov/; NCT01109849.

A Randomized Clinical Trial of an Integrative Group Therapy for Children With Severe Mood Dysregulation.

OBJECTIVE: Nonepisodic irritability is a common and impairing problem, leading to the development of the diagnoses severe mood dysregulation (SMD) and disruptive mood dysregulation disorder (DMDD). No psychosocial therapies have been formally evaluated for either, with medication being the most common treatment. This study examined the feasibility and efficacy of a joint parent-child intervention for SMD. METHOD: A total of 68 participants aged 7 to 12 years with attention-deficit/hyperactivity disorder (ADHD) and SMD were randomly assigned to the 11-week therapy or community-based psychosocial treatment. All participants were first stabilized on psychostimulant medication by study physicians. Of the participants, 56 still manifested impairing SMD symptoms and entered the therapy phase. Masked evaluators assessed participants at baseline, midpoint, and endpoint, with therapy participants reassessed 6 weeks later. RESULTS: All but 2 therapy participants attended the majority of sessions (n = 29), with families reporting high levels of satisfaction. The primary outcome of change in mood symptoms using the Mood Severity Index (MSI) did not reach significance except in the subset attending the majority of sessions (effect size = 0.53). Therapy was associated with significantly greater improvement in parent-rated irritability (effect size = 0.63). Treatment effects for irritability but not MSI diminished after therapy stopped. Little impact on ADHD symptoms was seen. Results may not be generalizable to youth with SMD and comorbidities different from those seen in this sample of children with ADHD, and are limited by the lack of a gold standard for measuring change in SMD symptoms. CONCLUSION: While failing to significantly improve mood symptoms versus community treatment, the integrative therapy was found to be a feasible and efficacious treatment for irritability in participants with SMD and ADHD. CLINICAL TRIAL REGISTRATION INFORMATION: Group-Based Behavioral Therapy Combined With Stimulant Medication for Treating Children With Attention Deficit Hyperactivity Disorder and Impaired Mood; http://clinicaltrials.gov/; NCT00632619.